What videogames would you be playing back in the days? As more than half of all cancers are diagnosed in people 65 years and older, determining whether CDK4/6 therapeutics exacerbate age-related disease will be of significant interest. Don’t forget to share the info with your friends, loved ones, or social media followers. Here, the HPV viral oncoprotein, E7, functionally inactivates RB leading to increases in p16INK4a expression (124). The induction of senescence and p16INK4a expression is traditionally associated with a wide variety of intrinsic cellular stressors including: DNA damage, telomere erosion, ROS, and stalled replication forks (reviewed in ref. (Sponsored link; 18+ only). Subsequently, ANRIL binding to SUZ12, a component of the PRC2 complex, was reported to promote silencing of p15INK4b, but not p16INK4a (50). Although loss of Hdac1, 2, 3, or 4 causes developmental abnormalities and lethality in mice, none of these phenotypes have been attributed to defects in p16INK4a regulation (90). Alterations in the p16INK4a tumor suppressor pathway are frequent in human cancer. This viral craze started in 2013 and gets resurrected now and then. It represents justice, nurturing and responsibility. View the complete list of February 29 historical events. A study by Negishi and colleagues showed that reductions in ZFP277 expression caused by oxidative stress could lead to PRC1 dissociation from the p16INK4a promoter and subsequent cell-cycle arrest (54). 142). This action is directly antagonized by ID1, which prevents the interaction of ETS1, ETS2, and E47 with the p16INK4a promoter (67, 68). For example, in the presence of oxidative stress, NSUN2 levels appear to increase, tipping the balance toward mRNA stability, p16INK4a expression, and subsequent cell-cycle arrest (111). For example, pancreatic intraepithelial neoplasias frequently inactivate p16INK4a upon progression to invasive disease (122). Check your answers here: Word scramble ASRKYUAFDS. One model proposes that the activity of distal enhancer elements is modified by SNP genotype (165). 1924) 2000 – Charles M. Schulz, American cartoonist, created Peanuts (b. Con quali videogame giocavi probabilmente in quei giorni? Indeed, p16INK4a levels do not seem to influence the regenerative capacity of murine melanocyte stem cells or neuronal progenitors of the dentate gyrus (unpublished observations and refs 153, 157). The day of the week of your birthday this year was Saturday. February is named after the Latin word februum, or maybe even the more ancient februa, which was a spring festival of washing and purification. You might be happy to know that the following celebrities share your birthday. Next year it will be Monday and two years from now it will be Tuesday. Child labor: In South Carolina, the minimum working age for factory, mill, and mine workers is raised from twelve to fourteen years old. Moreover, skin biopsies from long-lived nonagenarian cohorts have fewer p16INK4a-positive cells than their age-matched partners (146). Since the discovery of p16INK4a >20 years ago, numerous advances have led to an increasingly complex view of p16INK4a regulation and function. JMJD3 demethylates H3K27me3 and subsequent chromatin decondensation promotes access by transcription factors and p16INK4a transcription whereas JDP2 binds H3K27 and prevents further methylation. Earlier, we discussed the potential for neoplastic transformation to initiate cell nonautonomous p16INK4a expression. Several lines of evidence suggest that p16INK4a is not only a biomarker of aging, but also causes aging in many cell types. A leap year has 366 days, as opposed to a common year, which has 365. 5B). GWAS have implicated 9p21.3 SNPs in cancer, heart disease, glaucoma, type 2 diabetes, autism, and endometriosis. 67). Therefore, precise regulation of p16INK4a is essential to tissue homeostasis, maintaining a coordinated balance between tumor suppression and aging. Specifically, expression of p16INK4a has been reported to stabilize p21CIP1, and may inhibit the AUF1-dependent decay of p21CIP1, cyclin D1, and e2f1 mRNA (27, 28). On February 29, 2000 Pope St John Paul II was leading the Catholic Church. But much more happened that day: find out below.. You can also have a look at the year 2000, at February 29 across the years or at February 2000 calendar. With only 28 days in common years and 29 days in leap years, February is the shortest month of the year. In their studies of cancer cell lines, knockdown of CTCF resulted in the spread of heterochromatin DNA into the INK4/ARF locus, leading to epigenetic silencing of p16INK4a (65). By using such alleles to delete Ezh2 in the brain, pancreas, and embryonic skin, phenotypic outcomes have been observed. You should help others, bringing them spirit of joy. The next full moon that you can see will be on November 30 at 09:31:00 GMT – Monday. Repubblica.it 29 febbraio 2000 sez. 49). You spent 33% of your life sleeping. As a whole, these data provide evidence that the cell-cycle–related functions of p16INK4a may extend beyond CDK4/6 inhibition to include the regulation of other CDK-CYCLIN targets. 10). US date format: 2/29/2000, UK date format: 29/2/2000. 164). Of the identified SNPs, those that have been shown to correlate with CDKN2A expression in at least one study are filled with gray. 2A; ref. Regardless of the mechanism, these data make it clear that p16INK4a expression in the tumor stroma should not be ignored. Christopher Columbus uses his knowledge of a lunar eclipse that night to convince Native Americans to provide him with supplies. Although the mechanism has yet to be defined, six other homeobox-containing proteins (HOXA9, DLX3, HOXB13, HOXC13, HOXD3, and HOXD8) were similarly reported to participate in p16INK4a silencing (52). Februar (de); 29 февраля (ru); 29 ñiqin hatun puquy killapi (qu); २९ फरबरी (mai); 29 февраль (ce); Pebreru 29 (pam); 29. únor (cs); 29 febrewaori (nds-nl); 29'ê reşemiyê (ku); २९ फेब्रुअरी (ne); Fepuari 29 (sm); 29. As such, it is not surprising that p27KIP1 deletion can rescue the retinal hypoplasia and early mortality phenotypes of Cyclin D1-null mice (20, 21). In this book, Cokie and Steve discuss issues of their own marriage, Independently wealthy eco-terrorist Twilly Spree teaches a flagrant litterbug a lesson--and leaves the offender's precious Range Rover swarming with hungry dung beetles. Intense activation of the p16INK4a promoter is believed to represent a futile attempt by the cell to curb oncogenic proliferation in the absence of a functional G1–S checkpoint. Multiple variants of the PRC1 complex have been identified in vivo, each containing homologs of the Drosophila Posterior Sex Comb (Psc; NSPC1/PCGF1, MEL-18/PCGF2, RNF3/PCGF3, BMI1/PCGF4, RNF159/PCGF5, RNF134/PCGF6), Polycomb (Pc; CBX2, CBX4, CBX6, CBX7, CBX8), Sex Combs Extra (RING1, RING2), and Polyhomeotic proteins (Ph; HPH1, HPH2, HPH3; ref. Nothing to buy! Quali sono stati gli avvenimenti più importanti il 29 Febbraio 2000 ? The list was randomly chosen and arranged in chronological order. Rapporto attività solare Rapporto geofisico Regioni con macchie solari Valori Kp Flares solari Tempeste di radiazioni Vento solare (Velocità, Densità), Campo Magnetico Interplanetario (IMF) (Bt, Bz) Therefore, it appears that alterations in the milieu surrounding a growing neoplasm can promote the expression of p16INK4a in a cell-nonautonomous fashion (Fig. This process, known as “CDK inhibitor re-shuffling”, has been documented in a growing list of cell lines, and several lines of evidence support the biologic relevance of this model. with the most frank answers. 6261 - Bologna - Lapide 1530, cortile di Palazzo d'Accursio - Foto Giovanni Dall'Orto, 9-Feb-2008.jpg 1,554 × 1,354; 1.33 MB Did I mention it’s F-R-E-E? A, injection of Lkb1-null endometrial cancer cells into a syngenic mouse heterozygous for the p16LUC reporter causes stromal luciferase expression upon tumor growth. Proteins predicted to share a common binding site are depicted on top of one another. We probed 16 tumor types to determine the percentage of cases wherein mutational and/or copy-number changes disrupted genes critical to the p16INK4a tumor suppressor pathway (i.e., RB1, CDKN2A, CCND1 (CYCLIN D1), CCND2 (CYCLIN D2), CCND3 (CYCLIN D3), CCNE1 (CYCLIN E1), and CCNE2 (CYCLIN E2)). This incredible sensitivity, along with the observation that tumors maintained luciferase activity during progression, led to the hypothesis that p16INK4a transcription is activated in the surrounding tumor stroma. Try to imagine if all of them are crying at the same time. February 29, 2000 was a Tuesday and it was the 60th day of the year 2000. 130.) For the boys it’s Jacob. Other mechanisms of curbing age-related p16INK4a induction have been reported in mice. The numbers below each binding site indicate the position of protein interaction relative to the p16INK4a transcriptional start site. Dynamic induction of p16INK4a is observed during mammary involution, wound healing, nerve regeneration, and infection (unpublished data and refs 130, 172–174). This work was supported by NIH R00AG036817 (C.E. Who knows, they might appreciate and thank you for it. These data suggest that, in at least a subset of cell types, the kinase activity of CDK4/6 is predominantly responsible for proliferative control. Combining these genetic and epigenetic data suggests that functional inactivation of the p16INK4a–RB axis approaches 100% in many cancer types. Maintenance of this repression may be partially dependent on the ubiquitin-specific protease, USP11, which was also shown by Maertens and colleagues to bind and stabilize the PRC1 complex (34). As noted first by Sherr and colleagues (139), p16INK4a levels increase with aging. It is now known that these nuclear receptors directly bind and activate the p16INK4a promoter leading to subsequent cell-cycle arrest (91, 92). Proteins reported to transactivate EZH2, leading to PRC-mediated silencing of p16INK4a are depicted. Many of these phenotypes are attributable to the deregulation of homeobox gene expression; however, the lymphoid and neurologic defects observed in Bmi1 KO mice can be almost completely rescued by INK4/ARF deletion (36). Lastly, the birthday stone for the day of the week ‘Tuesday’ is ruby. The gene encoding p16INK4a, CDKN2A, lies within the INK4/ARF tumor suppressor locus on human chromosome 9p21.3 (Fig. Workers for the Good Lord, directed by Jean-Claude Brisseau, was one of the most viewed movies released in 2000 After a while, the Julian calendar and important religious holidays, like Easter, were several days out of sync with the fixed dates for astronomical events like equinoxes and solstices. On February 29, 2000 the UK Prime Minister was Tony Blair (Labour). Publisher: Cryo Interactive DreamCatcher Interactive, Publisher: Hasbro Interactive Mind's Eye Productions Namco, Publisher: Nintendo Microsoft Game Studios (X360). C, methylation of CDKN2A (black bars) and RB1 (gray bars) was quantified using HM27 or HM450 TCGA data. Similar to ID1, TWIST1 is reported to oppose transcriptional activation of p16INK4a. Single-nucleotide polymorphisms (SNP) in chromosome 9p21.3 have been linked to cancer, atherosclerosis, diabetes, frailty, cataracts. In response to oncogenic and senescent signaling, ETS1, ETS2, and/or E47 bind to E-box motifs (CANNTG) within the p16INK4a promoter to stimulate gene expression (67, 68). Rotazione precedente Giorno precedente Calendario. (CNN), Charlotte Hornets - Minnesota Timberwolves : 92 - 87, Chicago Bulls - Toronto Raptors : 80 - 87, Dallas Mavericks - Philadelphia 76ers : 87 - 106, Detroit Pistons - Indiana Pacers : 105 - 115, Los Angeles Lakers - Portland Trail Blazers : 90 - 87, International Business Machines IBM: opens at $105.56. In contrast, p18INK4c KOs are characterized by organomegaly; yet, the association of p27KIP1 with CDK2 complexes is unchanged in these animals (26). That’s equivalent to 248 babies every minute. Further work by this group showed that both muscle and adipocyte progenitors from these mice express high levels of p16INK4a, suggesting that even the deletion of senescent stem cells can promote improved regenerative capacity (156). This left February, the last month of the year, with the remaining 28 days. Understanding the role of p16INK4a in normal physiology will be critical to the development of “senolytic” therapies, which aim to lengthen our healthspan by eliminating senescent cells in the body. ricevi la mappa del cielo in questo giorno, Un regalo personalizzato con 29 Febbraio 2000, Sfoglia i giornali americani del 29 Febbraio 2000, Missy "Misdemeanor" Elliott Featuring NAS, EVE & Q-Tip, Trova il numero di LIFE del 29 Febbraio 2000, comincia il tuo periodo di prova di 30 giorni gratis, Giornali inglesi del passato del 29 Febbraio 2000, Vedi tutti i risultati delle partite di Basketball del 29 Febbraio 2000, Vedi tutti i risultati delle partite di Football del 29 Febbraio 2000. The observation that p16INK4a levels are high in senescent cells has prompted several investigations into the connection between prosenescent signaling and p16INK4a regulation. 4; refs 112–118). A, p16INK4a is negatively regulated by the histone-modifying complexes, PRC1 and PRC2, which combine to lay down repressive marks (e.g., H3K27me3, H2AK119ub) throughout the INK4/ARF locus. Flavopiridol (alvocidib) was originally touted as an inhibitor of EGF receptor (EGFR), but later was shown to inhibit the growth of a wide range of cancer cells at an IC50 much lower than that required to block EGFR activation. When is the next Leap Year? We do not retain these email addresses. World War II: The Admiralty Islands are invaded in Operation Brewer led by American General Douglas MacArthur. Therefore, therapeutic mimetics could have similar, detrimental consequences on the tumor microenvironment. From that point forward a small-sized dog like Jubil will age 4 dog years for every human year. This review outlines the molecular pathways critical for proper p16INK4a regulation and emphasizes the indispensable functions of p16INK4a in cancer, aging, and human physiology that make this gene special. With only 28 days in common years and 29 days in leap years, February is the shortest month of the year. (Sponsored by WordFinder.Cafe). Broad inhibition of CDKs, including CDK4 (IC50 < 120 nmol/L), was later identified as the mechanism of flavopiridol action (134). 32). Discover how the world looked like in 2000, Takemeback.to is a project by Time Machine S.R.L., Via Aurelio Saffi, 7 - 20123 Milan (Italy) - VAT/C.F./P.IVA IT11058110963. Thank you for sharing this Molecular Cancer Research article. It’s a fun and easy-to-play mobile game for all ages. Viene pubblicata la versione 1.0.0 del software R; Charlotte Hornets - Minnesota Timberwolves : 92 - 87, Chicago Bulls - Toronto Raptors : 80 - 87, Dallas Mavericks - Philadelphia 76ers : 87 - 106, Detroit Pistons - Indiana Pacers : 105 - 115, Los Angeles Lakers - Portland Trail Blazers : 90 - 87, International Business Machines IBM: opens at $105,56. Importantly, loss of p16INK4a is one of the most frequent events in human tumors and allows precancerous lesions to bypass senescence. Subscribe and get all 16 sample reports in one mega package. February is considered the seasonal equivalent of August in the opposite hemisphere. Your profession was shepherd, horseman, forester. ISSN: 1541-7786, Sign In to Email Alerts with your Email Address. For this reason, conditional KO alleles are required to assess the biologic functions of PRC2. Such increases in p16INK4a are exponential, increasing approximately 16-fold during the average human lifespan and making p16INK4a one of the most robust aging biomarkers characterized to date (141). Here’s a birthday wish just for you! Starring: Michael Douglas, Tobey Maguire, Frances McDormand, Robert Downey Jr. Be funny! Reconciliation of these two results is possible as rapid p16INK4a induction following CTCF knockdown would place enormous pressure on would-be cancer cells to epigenetically silence the INK4/ARF locus. Subunit rearrangement of the cyclin-dependent kinases is associated with cellular transformation, A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4, p15INK4B is a potential effector of TGF-beta-induced cell cycle arrest, Alternative reading frames of the INK4a tumor suppressor gene encode two unrelated proteins capable of inducing cell cycle arrest, The Ink4a tumor suppressor gene product, p19Arf, interacts with MDM2 and neutralizes MDM2′s inhibition of p53, ARF promotes MDM2 degradation and stabilizes p53: ARF-INK4a locus deletion impairs both the Rb and p53 tumor suppression pathways, A threshold mechanism mediates p53 cell fate decision between growth arrest and apoptosis, Characterization of a germ-line deletion, including the entire INK4/ARF locus, in a melanoma-neural system tumor family: identification of ANRIL, an antisense noncoding RNA whose expression coclusters with ARF, Epigenetic silencing of tumour suppressor gene p15 by its antisense RNA, Molecular interplay of the noncoding RNA ANRIL and methylated histone H3 lysine 27 by polycomb CBX7 in transcriptional silencing of INK4a, Kip/Cip and Ink4 Cdk inhibitors cooperate to induce cell cycle arrest in response to TGF-beta, New functional activities for the p21 family of CDK inhibitors, The p21(Cip1) and p27(Kip1) CDK ‘inhibitors' are essential activators of cyclin D-dependent kinases in murine fibroblasts, Requirement of cyclin E-Cdk2 inhibition in p16(INK4a)-mediated growth suppression, CDK inhibitors: positive and negative regulators of G1-phase progression, CDK2 activation in mouse epidermis induces keratinocyte proliferation but does not affect skin tumor development, Cyclin D1-dependent kinase activity in murine development and mammary tumorigenesis, CDK6 kinase activity is required for thymocyte development, The LxCxE pRb interaction domain of cyclin D1 is dispensable for murine development, Deletion of the p27Kip1 gene restores normal development in cyclin D1-deficient mice, Genetic evidence for the interactions of cyclin D1 and p27(Kip1) in mice, Wide spectrum of tumors in knock-in mice carrying a Cdk4 protein insensitive to INK4 inhibitors, INK4d-deficient mice are fertile despite testicular atrophy, Limited overlapping roles of P15(INK4b) and P18(INK4c) cell cycle inhibitors in proliferation and tumorigenesis, Loss of p16Ink4a with retention of p19Arf predisposes mice to tumorigenesis, CDK inhibitors p18(INK4c) and p27(Kip1) mediate two separate pathways to collaboratively suppress pituitary tumorigenesis, p16(INK4A) positively regulates p21(WAF1) expression by suppressing AUF1-dependent mRNA decay, p16(INK4a) positively regulates cyclin D1 and E2F1 through negative control of AUF1, The Polycomb complex PRC2 and its mark in life, SUZ12 is required for both the histone methyltransferase activity and the silencing function of the EED-EZH2 complex, The Polycomb group proteins bind throughout the INK4A-ARF locus and are disassociated in senescent cells, Several distinct polycomb complexes regulate and co-localize on the INK4a tumor suppressor locus, A “complex” issue: deciphering the role of variant PRC1 in ESCs, Ubiquitin-specific proteases 7 and 11 modulate Polycomb regulation of the INK4a tumour suppressor, Posterior transformation, neurological abnormalities, and severe hematopoietic defects in mice with a targeted deletion of the bmi-1 proto-oncogene, The oncogene and Polycomb-group gene bmi-1 regulates cell proliferation and senescence through the ink4a locus, Differential impact of Ink4a and Arf on hematopoietic stem cells and their bone marrow microenvironment in Bmi1-deficient mice, Bmi-1 dependence distinguishes neural stem cell self-renewal from progenitor proliferation, The polycomb-group gene Ezh2 is required for early mouse development, Suz12 is essential for mouse development and for EZH2 histone methyltransferase activity, Polycomb protein Ezh2 regulates pancreatic beta-cell Ink4a/Arf expression and regeneration in diabetes mellitus, Ezh2, the histone methyltransferase of PRC2, regulates the balance between self-renewal and differentiation in the cerebral cortex, EZH1 and EZH2 cogovern histone H3K27 trimethylation and are essential for hair follicle homeostasis and wound repair, The NSD1 and EZH2 overgrowth genes, similarities and differences, Coordinated activities of wild-type plus mutant EZH2 drive tumor-associated hypertrimethylation of lysine 27 on histone H3 (H3K27) in human B-cell lymphomas, Somatic mutations of the histone methyltransferase gene EZH2 in myelodysplastic syndromes, Epigenetic antagonism between polycomb and SWI/SNF complexes during oncogenic transformation, Durable tumor regression in genetically altered malignant rhabdoid tumors by inhibition of methyltransferase EZH2, Mechanisms of polycomb gene silencing: knowns and unknowns, Long non-coding RNA ANRIL is required for the PRC2 recruitment to and silencing of p15(INK4B) tumor suppressor gene, Role for the MOV10 RNA helicase in polycomb-mediated repression of the INK4a tumor suppressor, Interplay between Homeobox proteins and Polycomb repressive complexes in p16INK(4)a regulation, Ndy1/KDM2B immortalizes mouse embryonic fibroblasts by repressing the Ink4a/Arf locus, A novel zinc finger protein Zfp277 mediates transcriptional repression of the Ink4a/arf locus through polycomb repressive complex 1, pRB family proteins are required for H3K27 trimethylation and Polycomb repression complexes binding to and silencing p16INK4alpha tumor suppressor gene, EZH2 is downstream of the pRB-E2F pathway, essential for proliferation and amplified in cancer, Activated p53 suppresses the histone methyltransferase EZH2 gene, The H3K27me3 demethylase JMJD3 contributes to the activation of the INK4A-ARF locus in response to oncogene- and stress-induced senescence, Histone demethylase JMJD3 contributes to epigenetic control of INK4a/ARF by oncogenic RAS, JDP2 (Jun Dimerization Protein 2)-deficient mouse embryonic fibroblasts are resistant to replicative senescence, The Ink4/Arf locus is a barrier for iPS cell reprogramming, Jmjd3 inhibits reprogramming by upregulating expression of INK4a/Arf and targeting PHF20 for ubiquitination, P16INK4a is required for hSNF5 chromatin remodeler-induced cellular senescence in malignant rhabdoid tumor cells, SWI/SNF mediates polycomb eviction and epigenetic reprogramming of the INK4b-ARF-INK4a locus, Epigenetic silencing of the p16(INK4a) tumor suppressor is associated with loss of CTCF binding and a chromatin boundary, Quantitative assessment of higher-order chromatin structure of the INK4/ARF locus in human senescent cells, Opposing effects of Ets and Id proteins on p16INK4a expression during cellular senescence, Regulation of cellular senescence and p16(INK4a) expression by Id1 and E47 proteins in human diploid fibroblast, Id1 regulation of cellular senescence through transcriptional repression of p16/Ink4a, Ink4a/Arf expression is a biomarker of aging, BRAFE600-associated senescence-like cell cycle arrest of human naevi, Induction of EMT by twist proteins as a collateral effect of tumor-promoting inactivation of premature senescence, Twist-1 induces Ezh2 recruitment regulating histone methylation along the Ink4A/Arf locus in mesenchymal stem cells, JunB suppresses cell proliferation by transcriptional activation of p16(INK4a) expression, The c-Jun NH2-terminal kinase 2 plays a dominant role in human epidermal neoplasia, Over-expression of Id-1 induces cell proliferation in hepatocellular carcinoma through inactivation of p16INK4a/RB pathway, c-Jun regulates eyelid closure and skin tumor development through EGFR signaling, The transcriptional repressor of p16/Ink4a, Id1, is up-regulated in early melanomas, VentX trans-activates p53 and p16ink4a to regulate cellular senescence, A functional screen for regulators of CKDN2A reveals MEOX2 as a transcriptional activator of INK4a, Mechanisms of MEOX1 and MEOX2 regulation of the cyclin dependent kinase inhibitors p21 and p16 in vascular endothelial cells, A p16INK4a-insensitive CDK4 mutant targeted by cytolytic T lymphocytes in a human melanoma, The acetylation of transcription factor HBP1 by p300/CBP enhances p16INK4A expression, P300 plays a role in p16(INK4a) expression and cell cycle arrest, B-MYB delays cell aging by repressing p16 (INK4alpha) transcription, Effects of B-Myb on gene transcription: phosphorylation-dependent activity ans acetylation by p300, The transcription factor ZBP-89 suppresses p16 expression through a histone modification mechanism to affect cell senescence, Targeted inactivation of HDAC2 restores p16INK4a activity and exerts antitumor effects on human gastric cancer, Senescence delay and repression of p16INK4a by Lsh via recruitment of histone deacetylases in human diploid fibroblasts, The many roles of histone deacetylases in development and physiology: implications for disease and therapy, PPAR{gamma} accelerates cellular senescence by inducing p16INK4{alpha} expression in human diploid fibroblasts, PPAR alpha inhibits vascular smooth muscle cell proliferation underlying intimal hyperplasia by inducing the tumor suppressor p16INK4a, Imbalance between pSmad3 and Notch induces CDK inhibitors in old muscle stem cells, Aging of signal transduction pathways, and pathology, Beta-catenin induces immortalization of melanocytes by suppressing p16INK4a expression and cooperates with N-Ras in melanoma development, Induction of p16INK4A mediated by beta-catenin in a TCF4-independent manner: implications for alterations in p16INK4A and pRb expression during trans-differentiation of endometrial carcinoma cells, p16INK4a is a beta-catenin target gene and indicates low survival in human colorectal tumors, Wnt/beta-catenin signaling induces the aging of mesenchymal stem cells through promoting the ROS production, Primary cilium-dependent and -independent Hedgehog signaling inhibits p16(INK4A), Arp2/3 is critical for lamellipodia and response to extracellular matrix cues but is dispensable for chemotaxis, p16(INK4a) translation suppressed by miR-24, MicroRNA miR-24 promotes cell proliferation by targeting the CDKs inhibitors p27 and p16, The nuclear envelope can control gene expression and cell cycle progression via miRNA regulation, miR-24 Inhibits cell proliferation by targeting E2F2, MYC, and other cell-cycle genes via binding to “seedless” 3′UTR microRNA recognition elements, Regulation of p14ARF expression by miR-24: a potential mechanism compromising the p53 response during retinoblastoma development, A pleiotropically acting microRNA, miR-31, inhibits breast cancer metastasis, Hmga2 promotes neural stem cell self-renewal in young but not old mice by reducing p16Ink4a and p19Arf Expression, Let-7 and miR-200 microRNAs: guardians against pluripotency and cancer progression, HuR uses AUF1 as a cofactor to promote p16INK4 mRNA decay, The tRNA methyltransferase NSun2 stabilizes p16INK(4) mRNA by methylating the 3′-untranslated region of p16, The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data, Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal, Integrated genomic analyses of ovarian carcinoma, Comprehensive molecular portraits of human breast tumours, Comprehensive genomic characterization defines human glioblastoma genes and core pathways, Comprehensive genomic characterization of squamous cell lung cancers, Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia, Absence of p16INK4 protein is restricted to the subset of lung cancer lines that retains wildtype RB, Molecular classification and molecular genetics of human lung cancers, Abrogation of the Rb/p16 tumor-suppressive pathway in virtually all pancreatic carcinomas, The meaning of p16(ink4a) expression in tumors: functional significance, clinical associations and future developments, Adenovirus E1A, simian virus 40 tumor antigen, and human papillomavirus E7 protein share the capacity to disrupt the interaction between transcription factor E2F and the retinoblastoma gene product, Expression of p16 and lack of pRB in primary small cell lung cancer, Most basal-like breast carcinomas demonstrate the same Rb-/p16+ immunophenotype as the HPV-related poorly differentiated squamous cell carcinomas which they resemble morphologically, Prognostic value of p16 in locally advanced prostate cancer: a study based on Radiation Therapy Oncology Group Protocol 9202, Overexpression of the cyclin-dependent kinase inhibitor p16 is associated with tumor recurrence in human prostate cancer, Prognostic significance of p16INK4A and human papillomavirus in patients with oropharyngeal cancer treated on TROG 02.02 phase III trial, Monitoring tumorigenesis and senescence in vivo with a p16(INK4a)-luciferase model, CDK inhibitors (p16/p19/p21) induce senescence and autophagy in cancer-associated fibroblasts, “fueling” tumor growth via paracrine interactions, without an increase in neo-angiogenesis, Association of RB/p16-pathway perturbations with DCIS recurrence: dependence on tumor versus tissue microenvironment, The CDK inhibitors in cancer research and therapy, Flavopiridol induces G1 arrest with inhibition of cyclin-dependent kinase (CDK) 2 and CDK4 in human breast carcinoma cells, Phase II study of flavopiridol in relapsed chronic lymphocytic leukemia demonstrating high response rates in genetically high-risk disease, Cyclin-dependent kinase inhibitors move into Phase III, Blockbuster dreams for Pfizer's CDK inhibitor, Selective CDK4/6 inhibition with tumor responses by PD0332991 in patients with mantle cell lymphoma, Expression of the p16INK4a tumor suppressor versus other INK4 family members during mouse development and aging, The regulation of INK4/ARF in cancer and aging, Expression of p16(INK4a) in peripheral blood T-cells is a biomarker of human aging, Tumor suppressor mechanisms in immune aging, Gene expression profiling of aging reveals activation of a p53-mediated transcriptional program, Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders, The number of p16INK4a positive cells in human skin reflects biological age, Expression of p16(INK4a) as a biomarker of T-cell aging in HIV-infected patients prior to and during antiretroviral therapy, Effects of donor age and cell senescence on kidney allograft survival, Cellular senescence in pretransplant renal biopsies predicts postoperative organ function, Markers of cellular senescence in zero hour biopsies predict outcome in renal transplantation, Stem-cell ageing modified by the cyclin-dependent kinase inhibitor p16INK4a, p16INK4a induces an age-dependent decline in islet regenerative potential, Increasing p16INK4a expression decreases forebrain progenitors and neurogenesis during ageing, Expression of p16(INK4a) prevents cancer and promotes aging in lymphocytes, Bmi-1 regulates the Ink4a/Arf locus to control pancreatic beta-cell proliferation, p21 both attenuates and drives senescence and aging in BubR1 progeroid mice, Genotoxic stress abrogates renewal of melanocyte stem cells by triggering their differentiation, PDGF signalling controls age-dependent proliferation in pancreatic beta-cells, Fibroblast growth factor-7 partially reverses murine thymocyte progenitor aging by repression of Ink4a, Cellular senescence and the senescent secretory phenotype: therapeutic opportunities, Senescence impairs successful reprogramming to pluripotent stem cells, Immortalization eliminates a roadblock during cellular reprogramming into iPS cells, Rejuvenating senescent and centenarian human cells by reprogramming through the pluripotent state, Review: a meta-analysis of GWAS and age-associated diseases, Functional analysis of the chromosome 9p21.3 coronary artery disease risk locus, Expression of linear and novel circular forms of an INK4/ARF-associated non-coding RNA correlates with atherosclerosis risk, Genetic mechanisms mediating atherosclerosis susceptibility at the chromosome 9p21 locus, Cdkn2a is an atherosclerosis modifier locus that regulates monocyte/macrophage proliferation, Targeted deletion of the 9p21 non-coding coronary artery disease risk interval in mice, p19(ARF) deficiency reduces macrophage and vascular smooth muscle cell apoptosis and aggravates atherosclerosis, Increased gene dosage of the Ink4/Arf locus does not attenuate atherosclerosis development in hypercholesterolaemic mice, A keratinocyte hypermotility/growth-arrest response involving laminin 5 and p16INK4A activated in wound healing and senescence, Regulation of cyclin D1 and p16(INK4A) is critical for growth arrest during mammary involution, Epigenetic induction of the Ink4a/Arf locus prevents Schwann cell overproliferation during nerve regeneration and after tumorigenic challenge, Role of NR4A1, NR4A2, and NR4A3 in Cancer, Cancer Epidemiology, Biomarkers & Prevention, Spotlight on Genomic Analysis of Rare and Understudied Cancers, The Molecular Balancing Act of p16INK4a in Cancer and Aging, Transcriptional, Translational, and Epigenetic Regulation of, Disclosure of Potential Conflicts of Interest.
Fidanzata Di Maurizio Merluzzo, Tommaso D'aquino Pensiero Filosofico, Zona Porta Ticinese Milano, Miglior Allergologo In Italia, Lettera Sulla Crisi Einstein, Papa Leone Aidone, Santa Maria Francesca Napoli Preghiera,