Gene Symbol: Cdkn2b
Description: cyclin dependent kinase inhibitor 2B
Alias: AV083695, INK4b, MTS2, p15, p15(INK4b), p15INK4b, cyclin-dependent kinase 4 inhibitor B, cyclin-dependent kinase inhibitor 2B (p15, inhibits CDK4), cyclin-dependent kinase inhibitor p15, cyclin-dependent kinase inhibitor p15INK4b, cyclin-dependent kinase inhibitor protein, p14-INK4b, p15-INK4b
Species: mouse
Products:     Cdkn2b

Top Publications

  1. Kusy S, Larsen C, Roche J. p14ARF, p15INK4b and p16INK4a methylation status in chronic myelogenous leukemia. Leuk Lymphoma. 2004;45:1989-94 pubmed
    The INK4 family of proteins p15INK4b, p14ARF and p16INK4a function as cell cycle inhibitors where they are involved in the inhibition of G1 phase progression...
  2. Krimpenfort P, IJpenberg A, Song J, van der Valk M, Nawijn M, Zevenhoven J, et al. p15Ink4b is a critical tumour suppressor in the absence of p16Ink4a. Nature. 2007;448:943-6 pubmed
    ..The locus encodes three cell cycle inhibitory proteins: p15INK4b encoded by CDKN2b, p16INK4a encoded by CDKN2a and p14ARF (p19Arf in mice) encoded by an alternative reading frame ..
  3. Spiller C, Wilhelm D, Koopman P. Retinoblastoma 1 protein modulates XY germ cell entry into G1/G0 arrest during fetal development in mice. Biol Reprod. 2010;82:433-43 pubmed publisher the Rb1(-/-) testes, but we saw a significant increase of cyclin-dependent kinase (CDK) inhibitor Cdkn1b and Cdkn2b expression...
  4. Latres E, Malumbres M, Sotillo R, Martin J, Ortega S, Martin Caballero J, et al. Limited overlapping roles of P15(INK4b) and P18(INK4c) cell cycle inhibitors in proliferation and tumorigenesis. EMBO J. 2000;19:3496-506 pubmed
    ..We report the generation of mice defective in P15(INK4b) and P18(INK4c)...
  5. Mattison J, Kool J, Uren A, de Ridder J, Wessels L, Jonkers J, et al. Novel candidate cancer genes identified by a large-scale cross-species comparative oncogenomics approach. Cancer Res. 2010;70:883-95 pubmed publisher
    ..Collectively, this work provides a rich catalogue of new candidate cancer genes for functional analysis. ..
  6. Trivedi C, Lu M, Wang Q, Epstein J. Transgenic overexpression of Hdac3 in the heart produces increased postnatal cardiac myocyte proliferation but does not induce hypertrophy. J Biol Chem. 2008;283:26484-9 pubmed publisher
    ..Hdac3 overexpression inhibits several cyclin-dependent kinase inhibitors, including Cdkn1a, Cdkn1b, Cdkn1c, Cdkn2b, and Cdkn2c...
  7. Le Chalony C, Hayes H, Frelat G, Geffrotin C. Identification and mapping of swine cyclin-dependent kinase inhibitor CDKN2A and CDKN2B exon 2 sequences. Cytogenet Cell Genet. 2000;88:240-3 pubmed
    We have isolated the swine homologs of human CDKN2A and CDKN2B exon 2 sequences. As in the human and mouse genomes, the exon 2 sequences of these two genes present a high level of sequence homology and are tightly linked...
  8. Magdaleno S, Wang G, Mireles V, Ray M, Finegold M, DeMayo F. Cyclin-dependent kinase inhibitor expression in pulmonary Clara cells transformed with SV40 large T antigen in transgenic mice. Cell Growth Differ. 1997;8:145-55 pubmed
    ..Increases in specific cyclin-dependent kinase inhibitor steady-state mRNA levels were detected in p15, p18, p27, and p57 during tumor progression...
  9. Herzog C, Soloff E, McDoniels A, Tyson F, Malkinson A, Haugen Strano A, et al. Homozygous codeletion and differential decreased expression of p15INK4b, p16INK4a-alpha and p16INK4a-beta in mouse lung tumor cells. Oncogene. 1996;13:1885-91 pubmed
    The genes of murine cyclin D-dependent kinase inhibitors, p15INK4b and p16INK4a, are located in a region of chromosome 4 where overlapping deletions were found in lung adenocarcinomas...

More Information


  1. Jimenez M, Perez de Castro I, Benet M, Garcia J, Inghirami G, Pellicer A. The Rgr oncogene induces tumorigenesis in transgenic mice. Cancer Res. 2004;64:6041-9 pubmed
    ..the overall incidence and latency of fibrosarcomas were substantially increased and shortened, respectively, in a p15INK4b-defective background...
  2. Collins C, Wang J, Miao H, Bronstein J, Nawer H, Xu T, et al. C/EBP? is an essential collaborator in Hoxa9/Meis1-mediated leukemogenesis. Proc Natl Acad Sci U S A. 2014;111:9899-904 pubmed publisher
    ..Together, our results suggest a previously unidentified role for C/EBP? in maintaining the proliferation required for Hoxa9/Meis1-mediated leukemogenesis. ..
  3. Rosu Myles M, Taylor B, Wolff L. Loss of the tumor suppressor p15Ink4b enhances myeloid progenitor formation from common myeloid progenitors. Exp Hematol. 2007;35:394-406 pubmed
    The tumor suppressor p15Ink4b (Ink4b) is a cell-cycle inhibitor that is inactivated in a high percentage of acute myeloid leukemia and myeloid dysplasia syndrome cases. Despite this, the role of Ink4b in hematopoiesis remains unclear...
  4. Ko R, Kim H, Wolff L, Klug C. Roles of p15Ink4b and p16Ink4a in myeloid differentiation and RUNX1-ETO-associated acute myeloid leukemia. Leuk Res. 2008;32:1101-11 pubmed
    Inactivation of p15(Ink4b) expression by promoter hypermethylation occurs in up to 80% of acute myeloid leukemia (AML) cases and is particularly common in the FAB-M2 subtype of AML, which is characterized by the presence of the RUNX1-ETO ..
  5. Schuster K, Venkateswaran N, Rabellino A, Girard L, Peña Llopis S, Scaglioni P. Nullifying the CDKN2AB locus promotes mutant K-ras lung tumorigenesis. Mol Cancer Res. 2014;12:912-23 pubmed publisher
    ..However, little is known regarding the function of p15INK4B translated from the same locus...
  6. Park J, Oh Y, Yoo L, Jung M, Song W, Lee S, et al. Dyrk1A phosphorylates p53 and inhibits proliferation of embryonic neuronal cells. J Biol Chem. 2010;285:31895-906 pubmed publisher
    ..These findings suggest that up-regulation of Dyrk1A contributes to altered neuronal proliferation in DS through specific phosphorylation of p53 at Ser-15 and subsequent p21(CIP1) induction. ..
  7. Schmidt M, Bies J, Tamura T, Ozato K, Wolff L. The interferon regulatory factor ICSBP/IRF-8 in combination with PU.1 up-regulates expression of tumor suppressor p15(Ink4b) in murine myeloid cells. Blood. 2004;103:4142-9 pubmed
    b>CDKN2B (INK4B), which encodes the cyclin-dependent kinase inhibitor p15(INK4b), is up-regulated by many cytokines found in hematopoietic environments in vivo. In human acute myeloid leukemias (AMLs), it is inactivated with high frequency...
  8. de Jaime Soguero A, Aulicino F, Ertaylan G, Griego A, Cerrato A, Tallam A, et al. Wnt/Tcf1 pathway restricts embryonic stem cell cycle through activation of the Ink4/Arf locus. PLoS Genet. 2017;13:e1006682 pubmed publisher
    ..but not Tcf3, is recruited to a palindromic motif enriched in the promoter of cell cycle repressor genes, such as p15Ink4b, p16Ink4a and p19Arf, which mediate the Wnt-dependent anti-proliferative effect in mESCs...
  9. Grange M, Giordano M, Mas A, Roncagalli R, Firaguay G, Nunes J, et al. Control of CD8 T cell proliferation and terminal differentiation by active STAT5 and CDKN2A/CDKN2B. Immunology. 2015;145:543-57 pubmed publisher shown using T cells from CDKN2A(-/-) mice) but was associated with expression of transcripts encoding p15(INK) (4B) , another protein involved in senescence induction...
  10. Malumbres M, Perez de Castro I, Santos J, Melendez B, Mangues R, Serrano M, et al. Inactivation of the cyclin-dependent kinase inhibitor p15INK4b by deletion and de novo methylation with independence of p16INK4a alterations in murine primary T-cell lymphomas. Oncogene. 1997;14:1361-70 pubmed
    A wide panel of murine induced T-cell lymphomas have been analysed for p16INK4a or p15INK4b alterations...
  11. Nanda V, Downing K, Ye J, Xiao S, Kojima Y, Spin J, et al. CDKN2B Regulates TGFβ Signaling and Smooth Muscle Cell Investment of Hypoxic Neovessels. Circ Res. 2016;118:230-40 pubmed publisher
    ..conditions, we performed femoral artery ligation surgery in mice lacking the 9p21 candidate gene, Cdkn2b. These animals developed advanced hindlimb ischemia and digital autoamputation, secondary to a defect in the ..
  12. Roussel M. The INK4 family of cell cycle inhibitors in cancer. Oncogene. 1999;18:5311-7 pubmed
  13. Western P, Ralli R, Wakeling S, Lo C, Van Den Bergen J, Miles D, et al. Mitotic arrest in teratoma susceptible fetal male germ cells. PLoS ONE. 2011;6:e20736 pubmed publisher
    ..In 129T2/SvJ mice germ cell mitotic arrest involves upregulation of p27(KIP1), p15(INK4B), activation of RB, the expression of male germ cell differentiation markers NANOS2, DNMT3L and MILI and ..
  14. Fukuda T, Tokunaga A, Sakamoto R, Yoshida N. Fbxl10/Kdm2b deficiency accelerates neural progenitor cell death and leads to exencephaly. Mol Cell Neurosci. 2011;46:614-24 pubmed publisher
    ..5 brain. Our findings suggest that the Fbxl10 gene makes important contributions to embryonic neural development by regulating cell proliferation and cell death in mice. ..
  15. Milstone Z, Lawson G, Trivedi C. Histone deacetylase 1 and 2 are essential for murine neural crest proliferation, pharyngeal arch development, and craniofacial morphogenesis. Dev Dyn. 2017;246:1015-1026 pubmed publisher
    ..Mechanistically, loss of Hdac1 and Hdac2 upregulates cyclin-dependent kinase inhibitors Cdkn1a, Cdkn1b, Cdkn1c, Cdkn2b, Cdkn2c, and Tp53 within the first pharyngeal arch...
  16. Tian X, Azpurua J, Ke Z, Augereau A, Zhang Z, Vijg J, et al. INK4 locus of the tumor-resistant rodent, the naked mole rat, expresses a functional p15/p16 hybrid isoform. Proc Natl Acad Sci U S A. 2015;112:1053-8 pubmed publisher
    ..This locus encodes three distinct tumor suppressors: p15(INK4b), p16(INK4a), and ARF (alternate reading frame)...
  17. Muscarella P, Knobloch T, Ulrich A, Casto B, Moniaux N, Wittel U, et al. Identification and sequencing of the Syrian Golden hamster (Mesocricetus auratus) p16(INK4a) and p15(INK4b) cDNAs and their homozygous gene deletion in cheek pouch and pancreatic tumor cells. Gene. 2001;278:235-43 pubmed
    ..Inactivation of the related p15(INK4b) gene has also been identified in a number of tumors and cell lines, however, its role as an independent tumor ..
  18. Kosaka Y, Cieslik K, Li L, Lezin G, Maguire C, Saijoh Y, et al. 14-3-3? plays a role in cardiac ventricular compaction by regulating the cardiomyocyte cell cycle. Mol Cell Biol. 2012;32:5089-102 pubmed publisher
    ..These data are consistent with the long-held view that human LVNC may result from compaction arrest, and they implicate 14-3-3? as a new candidate gene in congenital human cardiomyopathies. ..
  19. He A, Ma Q, Cao J, von Gise A, Zhou P, Xie H, et al. Polycomb repressive complex 2 regulates normal development of the mouse heart. Circ Res. 2012;110:406-15 pubmed publisher
    ..Our study reveals a previously undescribed role of EZH2 in regulating heart formation and shows that perturbation of the epigenetic landscape early in cardiogenesis has sustained disruptive effects at later developmental stages. ..
  20. You L, Yan K, Zou J, Zhao H, Bertos N, Park M, et al. The chromatin regulator Brpf1 regulates embryo development and cell proliferation. J Biol Chem. 2015;290:11349-64 pubmed publisher
    ..These results uncover a crucial role of Brpf1 in controlling mouse embryo development and regulating cellular and gene expression programs. ..
  21. Hannon G, Beach D. p15INK4B is a potential effector of TGF-beta-induced cell cycle arrest. Nature. 1994;371:257-61 pubmed
    ..2), which are inhibited by the protein p16INK4. We have isolated a new member of the p16INK4 family, p15INK4B. p15 expression is induced approximately 30-fold in human keratinocytes by treatment with TGF-beta, suggesting ..
  22. Pines J. Cyclin-dependent kinase inhibitors: the age of crystals. Biochim Biophys Acta. 1997;1332:M39-42 pubmed
  23. Sotillo R, Garcia J, Ortega S, Martin J, Dubus P, Barbacid M, et al. Invasive melanoma in Cdk4-targeted mice. Proc Natl Acad Sci U S A. 2001;98:13312-7 pubmed using targeted mice deficient for other INK4 inhibitors, we show that deletion of p18(INK4c) but not of p15(INK4b) confers proliferative advantage to melanocytic tumor growth...
  24. Yu H, Liu B, Costantini F, Hsu W. Impaired neural development caused by inducible expression of Axin in transgenic mice. Mech Dev. 2007;124:146-56 pubmed
    ..Our data support the conclusion that the development of embryonic neural axis is highly sensitive to the level of Wnt signaling. ..
  25. Angel J, Richie E. Tlag2, an N-methyl-N-nitrosourea susceptibility locus, maps to mouse chromosome 4. Mol Carcinog. 2002;33:105-12 pubmed
    ..Chromosome 4 has been associated with susceptibility to hematopoietic tumor development in several mouse models, suggesting that one or more genes mapping to this chromosome are important in lymphomagenesis in general. ..
  26. Wolff L, Garin M, Koller R, Bies J, Tessarollo L, Anver M, et al. A novel retrovirus provides the cooperating oncogenic event(s) required to demonstrate the tumor suppressor activity of p15Ink4b in myeloid cells in vivo. Blood Cells Mol Dis. 2004;32:226-31 pubmed
    ..we review these experiments and present examples of new models of myeloid leukemia where retroviruses have collaborated with a transgene [Cbfbeta-MYH111 from Inv(16)] and with loss of a tumor suppressor (Ink4b) mice to induce disease.
  27. Humeniuk R, Koller R, Bies J, Aplan P, Wolff L. Brief report: Loss of p15Ink4b accelerates development of myeloid neoplasms in Nup98-HoxD13 transgenic mice. Stem Cells. 2014;32:1361-6 pubmed publisher
    ..It has been shown recently that mice lacking p15Ink4b have skewed differentiation of common myeloid progenitors toward the myeloid lineage at the expense of erythroid ..
  28. Meng X, Zhang L, Chen X, Xiang Z, Li D, Han X. miR-541 Contributes to Microcystin-LR-Induced Reproductive Toxicity through Regulating the Expression of p15 in Mice. Toxins (Basel). 2016;8: pubmed publisher
    ..Our data support that p15 was the target gene of miR-541...
  29. Drosten M, Lechuga C, Barbacid M. Ras signaling is essential for skin development. Oncogene. 2014;33:2857-65 pubmed publisher
    ..These observations provide genetic evidence for an essential role of Ras proteins in the control of keratinocyte and epidermal proliferation. ..
  30. Okamura D, Maeda I, Taniguchi H, Tokitake Y, Ikeda M, Ozato K, et al. Cell cycle gene-specific control of transcription has a critical role in proliferation of primordial germ cells. Genes Dev. 2012;26:2477-82 pubmed publisher
    ..The expression of p15(INK4b), a cyclin-dependent kinase inhibitor (CDKI) gene, in PGCs is selectively activated by P-TEFb and its recruiting ..
  31. Adhikary S, Peukert K, Karsunky H, Beuger V, Lutz W, Elsässer H, et al. Miz1 is required for early embryonic development during gastrulation. Mol Cell Biol. 2003;23:7648-57 pubmed
    ..Miz1(-/-) embryos succumb to massive apoptosis of ectodermal cells around day 7.5 of embryonic development. Our results show that Miz1 is required for early embryonic development during gastrulation. ..
  32. Fares J, Koller R, Humeniuk R, Wolff L, Bies J. The tumor suppressor p15Ink4b regulates the differentiation and maturation of conventional dendritic cells. Blood. 2012;119:5005-15 pubmed publisher
    The tumor suppressor p15Ink4b is frequently inactivated by methylation in acute myeloid leukemia and premalignant myeloid disorders. Dendritic cells (DCs) as potent APCs play critical regulatory roles in antileukemic immune responses...
  33. Ferone G, Song J, Sutherland K, Bhaskaran R, Monkhorst K, Lambooij J, et al. SOX2 Is the Determining Oncogenic Switch in Promoting Lung Squamous Cell Carcinoma from Different Cells of Origin. Cancer Cell. 2016;30:519-532 pubmed publisher
    ..Our model highlights the essential role of SOX2 in commanding the squamous cell fate from different cells of origin and represents an invaluable tool for developing better intervention strategies. ..
  34. Vidal A, Koff A. Cell-cycle inhibitors: three families united by a common cause. Gene. 2000;247:1-15 pubmed
    ..We will discuss the interrelationships between Cip/Kip inhibitors and the components of the pRb pathway, and how their activities ultimately regulate cell proliferation. ..
  35. Yuan C, Li J, Selby T, Byeon I, Tsai M. Tumor suppressor INK4: comparisons of conformational properties between p16(INK4A) and p18(INK4C). J Mol Biol. 1999;294:201-11 pubmed
    The INK4 (inhibitor of cyclin-dependent kinase 4) family consists of four tumor-suppressor proteins: p15(INK4B), p16(INK4A), p18(INK4C), and p19(INK4D)...
  36. Jiang P, Stone S, Wagner R, Wang S, Dayananth P, Kozak C, et al. Comparative analysis of Homo sapiens and Mus musculus cyclin-dependent kinase (CDK) inhibitor genes p16 (MTS1) and p15 (MTS2). J Mol Evol. 1995;41:795-802 pubmed
    ..At least one of these molecules, p16, has been implicated in human tumorigenesis while its close homolog, p15, is induced by cell contact and transforming growth factor-beta (TGF-beta)...
  37. Muñoz Espín D, Canamero M, Maraver A, Gomez Lopez G, Contreras J, Murillo Cuesta S, et al. Programmed cell senescence during mammalian embryonic development. Cell. 2013;155:1104-18 pubmed publisher
    ..We conclude that the role of developmentally programmed senescence is to promote tissue remodeling and propose that this is the evolutionary origin of damage-induced senescence. ..
  38. Schmetsdorf S, Gärtner U, Arendt T. Expression of cell cycle-related proteins in developing and adult mouse hippocampus. Int J Dev Neurosci. 2005;23:101-12 pubmed
    ..Thus, they may have supplementary functions in differentiated neurons that might be associated with neuronal plasticity. ..
  39. Perez de Castro I, Benet M, Jimenez M, Alzabin S, Malumbres M, Pellicer A. Mouse p10, an alternative spliced form of p15INK4b, inhibits cell cycle progression and malignant transformation. Cancer Res. 2005;65:3249-56 pubmed
    ..Two of these cell cycle inhibitors, p16(INK4A) and p15(INK4B), have tumor suppressor activities and are inactivated in human cancer...
  40. Rodríguez Díez E, Quereda V, Bellutti F, Prchal Murphy M, Partida D, Eguren M, et al. Cdk4 and Cdk6 cooperate in counteracting the INK4 family of inhibitors during murine leukemogenesis. Blood. 2014;124:2380-90 pubmed publisher
    ..Our observations reveal that Cdk4 and Cdk6 cooperate in hematopoietic tumor development and suggest a role for Cdk6 in sequestering INK4 proteins away from Cdk4. ..
  41. Yu W, Gius D, Onyango P, Muldoon Jacobs K, Karp J, Feinberg A, et al. Epigenetic silencing of tumour suppressor gene p15 by its antisense RNA. Nature. 2008;451:202-6 pubmed publisher
    ..Here we show that many TSGs have nearby antisense RNAs, and we focus on the role of one RNA in silencing p15, a cyclin-dependent kinase inhibitor implicated in leukaemia...
  42. Malumbres M, Perez de Castro I, Santos J, Fernandez Piqueras J, Pellicer A. Hypermethylation of the cell cycle inhibitor p15INK4b 3'-untranslated region interferes with its transcriptional regulation in primary lymphomas. Oncogene. 1999;18:385-96 pubmed
    The cyclin-dependent kinase inhibitor p15INK4b has been shown to be involved in human and rodent tumors and seems to act as a tumor suppressor gene in hematological malignancies...
  43. Melendez B, Santos J, Fernandez Piqueras J. Loss of heterozygosity at the proximal-mid part of mouse chromosome 4 defines two novel tumor suppressor gene loci in T-cell lymphomas. Oncogene. 1999;18:4166-9 pubmed
    ..gene loci on the proximal-mid part of chromosome 4 and to clarify whether the p16(INK4a) (alpha and beta) and p15(INK4b) genes are the inactivation targets of deletion at TLSR1, we have tested 73 gamma-radiation-induced T-cell ..
  44. Tian J, Cao P, Yu X, Peng C, Yang X, Yan H. [mRNA expression and methylation status of p15 promoter in mouse bone marrow cells exposed to 1,4-benzoquinone]. Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi. 2011;29:28-32 pubmed
    To detect the expression and the CpG island methylation status of tumor suppressor gene p15 after exposure to 1,4-benzoquinone (1,4-BQ) in primary cultivated C57BL/6J mouse bone marrow cells in vitro...
  45. Haviernik P, Schmidt M, Hu X, Wolff L. Consistent inactivation of p19(Arf) but not p15(Ink4b) in murine myeloid cells transformed in vivo by deregulated c-Myc. Oncogene. 2003;22:1600-10 pubmed
    Cyclin-dependent kinase inhibitors p16(INK4a) and p15(INK4b), encoded by the CDKN2A and B loci, play an important role in negative regulation of the cell cycle...
  46. Peyre M, Stemmer Rachamimov A, Clermont Taranchon E, Quentin S, El Taraya N, Walczak C, et al. Meningioma progression in mice triggered by Nf2 and Cdkn2ab inactivation. Oncogene. 2013;32:4264-72 pubmed publisher
    ..The short latency of tumor development and the ability to derive grade II/III meningioma cell cultures are key aspects of this model to promote its use in pre-clinical drug testing. ..
  47. Malumbres M, Perez de Castro I, Santos J, Perez Olle R, Fernandez Piqueras J, Pellicer A. An AC-repeat adjacent to mouse Cdkn2B allows the detection of specific allelic losses in the p15INK4b and p16INK4a tumor suppressor genes. Mamm Genome. 1998;9:183-5 pubmed
    The cyclin-dependent kinase inhibitors p15INK4b and p16INK4a are involved in the development of a wide range of human and murine tumors...
  48. Inoue S, Hao Z, Elia A, Cescon D, Zhou L, Silvester J, et al. Mule/Huwe1/Arf-BP1 suppresses Ras-driven tumorigenesis by preventing c-Myc/Miz1-mediated down-regulation of p21 and p15. Genes Dev. 2013;27:1101-14 pubmed publisher the absence of Mule, c-Myc/Miz1 transcriptional complexes accumulated, and levels of p21CDKN1A (p21) and p15INK4B (p15) were down-regulated...
  49. Zindy F, Quelle D, Roussel M, Sherr C. Expression of the p16INK4a tumor suppressor versus other INK4 family members during mouse development and aging. Oncogene. 1997;15:203-11 pubmed
    ..Both p18INK4c and p19INK4d were widely expressed during mouse embryogenesis, but p16INK4a and p15INK4b were not readily detected prenatally...
  50. Linardopoulos S, Street A, Quelle D, Parry D, Peters G, Sherr C, et al. Deletion and altered regulation of p16INK4a and p15INK4b in undifferentiated mouse skin tumors. Cancer Res. 1995;55:5168-72 pubmed
    p16INK4a and p15INK4b are cell cycle regulators that specifically bind to and inhibit the cyclin D-dependent kinases, cdk4 and cdk6...
  51. Knoepfler P, Cheng P, Eisenman R. N-myc is essential during neurogenesis for the rapid expansion of progenitor cell populations and the inhibition of neuronal differentiation. Genes Dev. 2002;16:2699-712 pubmed
    ..progenitor cells also have comparatively high levels of the cdk inhibitors p27(Kip1) and p18(Ink4c), whereas p15(Ink4b), p21(Cip1), and p19(Ink4d) levels are unaffected...
  52. Zhang S, Ramsay E, Mock B. Cdkn2a, the cyclin-dependent kinase inhibitor encoding p16INK4a and p19ARF, is a candidate for the plasmacytoma susceptibility locus, Pctr1. Proc Natl Acad Sci U S A. 1998;95:2429-34 pubmed
    ..Restriction fragment length polymorphisms between BALB/c and DBA/2 for Cdkn2a(p16) and Cdkn2b(p15), and between BALB/c and Mus spretus for Cdkn2c(p18(INK4c)) were used to position these loci with respect to ..
  53. Liu Y, El Naggar S, Darling D, Higashi Y, Dean D. Zeb1 links epithelial-mesenchymal transition and cellular senescence. Development. 2008;135:579-88 pubmed publisher
    ..Instead, there is ectopic expression of two other cell cycle inhibitory cyclin-dependent kinase inhibitors, p15Ink4b (Cdkn2b) and p21Cdkn1a (Cdkn1a)...
  54. Monahan P, Himes A, Parfieniuk A, Raetzman L. p21, an important mediator of quiescence during pituitary tumor formation, is dispensable for normal pituitary development during embryogenesis. Mech Dev. 2012;128:640-52 pubmed publisher
    ..However, p21 may be required to maintain normal levels of cell cycle components. ..
  55. Wolff L, Garin M, Koller R, Bies J, Liao W, Malumbres M, et al. Hypermethylation of the Ink4b locus in murine myeloid leukemia and increased susceptibility to leukemia in p15(Ink4b)-deficient mice. Oncogene. 2003;22:9265-74 pubmed
    The Ink4b gene (Cdkn2b) encodes p15(Ink4b), a cyclin-dependent kinase inhibitor. It has been implicated in playing a role in the development of acute myeloid leukemia (AML) in man, since it is hypermethylated with high frequency...
  56. Lander J, Fan H. Low-frequency loss of heterozygosity in Moloney murine leukemia virus-induced tumors in BRAKF1/J mice. J Virol. 1997;71:3940-52 pubmed
    ..Candidate tumor suppressor genes, Mts1 (p16INK4a) and Mts2 (p15INK4b), have been mapped to this region, but by Southern blot analysis, no homozygous deletions were detected in either ..
  57. Fuster J, Molina Sánchez P, Jovaní D, Vinue A, Serrano M, Andres V. Increased gene dosage of the Ink4/Arf locus does not attenuate atherosclerosis development in hypercholesterolaemic mice. Atherosclerosis. 2012;221:98-105 pubmed publisher a block of high linkage disequilibrium with the neighboring Ink4/Arf tumor-suppressor locus (also named CDKN2A/CDKN2B)...
  58. Leeper N, Raiesdana A, Kojima Y, Kundu R, Cheng H, Maegdefessel L, et al. Loss of CDKN2B promotes p53-dependent smooth muscle cell apoptosis and aneurysm formation. Arterioscler Thromb Vasc Biol. 2013;33:e1-e10 pubmed publisher
    ..3, human expression quantitative trait locus studies have associated expression of the tumor suppressor gene CDKN2B with the risk haplotype, but its potential role in vascular pathobiology remains unclear...
  59. Spiller C, Feng C, Jackson A, Gillis A, Rolland A, Looijenga L, et al. Endogenous Nodal signaling regulates germ cell potency during mammalian testis development. Development. 2012;139:4123-32 pubmed publisher
    ..Thus, Nodal signaling provides a molecular control mechanism that regulates male germ cell potency in normal development and testicular cancer. ..
  60. Harrelson Z, Kelly R, Goldin S, Gibson Brown J, Bollag R, Silver L, et al. Tbx2 is essential for patterning the atrioventricular canal and for morphogenesis of the outflow tract during heart development. Development. 2004;131:5041-52 pubmed
    ..Despite evidence that TBX2 negatively regulates the cell cycle control genes Cdkn2a, Cdkn2b and Cdkn1a in cultured cells, there is no evidence that loss of Tbx2 function during mouse development results in ..
  61. Osei Sarfo K, de Castro I, Pellicer A. p15(INK4b) plays a crucial role in murine lymphoid development and tumorigenesis. Carcinogenesis. 2012;33:708-13 pubmed publisher
    To investigate if the cooperation between the Rgr oncogene and the inactivation of INK4b (a CDK inhibitor), as described previously in a sarcoma model, would be operational in a lymphoid system in vivo, we generated a transgenic/knockout ..
  62. Melendez B, Malumbres M, Perez de Castro I, Santos J, Pellicer A, Fernandez Piqueras J. Characterization of the murine p19(ARF) promoter CpG island and its methylation pattern in primary lymphomas. Carcinogenesis. 2000;21:817-21 pubmed
    ..DNA fragment with the characteristics of a CpG island similar to those described for the murine p16(INK4a) and p15(INK4b) genes. Expression of p19(ARF) is decreased in a significant number (20%) of the murine lymphomas analyzed...
  63. Camacho C, Todorova P, Hardebeck M, Tomimatsu N, Gil Del Alcazar C, Ilcheva M, et al. DNA double-strand breaks cooperate with loss of Ink4 and Arf tumor suppressors to generate glioblastomas with frequent Met amplification. Oncogene. 2015;34:1064-72 pubmed publisher
    ..mouse models harboring brain-targeted deletions of key tumor suppressors frequently lost in GBM, namely Ink4a, Ink4b, Arf and/or PTEN...
  64. Ait Oufella H, Herbin O, Lahoute C, Coatrieux C, Loyer X, Joffre J, et al. Group X secreted phospholipase A2 limits the development of atherosclerosis in LDL receptor-null mice. Arterioscler Thromb Vasc Biol. 2013;33:466-73 pubmed publisher
    ..Our results suggest that selective targeting of individual sPLA2 enzymes may be a better strategy to treat cardiovascular diseases. ..
  65. Gamell C, Gulati T, Levav Cohen Y, Young R, Do H, Pilling P, et al. Reduced abundance of the E3 ubiquitin ligase E6AP contributes to decreased expression of the INK4/ARF locus in non-small cell lung cancer. Sci Signal. 2017;10: pubmed publisher
    ..We found that the expression of three tumor suppressor genes encoded in the INK4/ARF locus (p15INK4b, p16INK4a, and p19ARF) was decreased in E6AP-/- mouse embryo fibroblasts...
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    ..Thus, the C terminus of p53 regulates gene expression via multiple mechanisms depending on the tissue and target, and this leads to specific phenotypic effects in vivo. ..
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    ..These genes include p15, p16, Rb, cyclin D1, p53, Apc, Mcc, and Gjal...
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    ..Loss of Nf2 and Cdkn2ab have synergistic effects with PDGF-B overexpression promoting meningioma malignant transformation. ..
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    ..Together, these findings establish TLX1 as a critical regulator of RA metabolism and provide mechanistic insights into the molecular determinants of human congenital asplenia. ..
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    Inactivation of p15INK4b, an inhibitor of cyclin-dependent kinases, through DNA methylation is one of the most common epigenetic abnormalities in myeloid leukemia...
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    ..No expression of two other INK4 members, p16INK4a and p15INK4b, was observed...
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    ..The murine cognates of these genes were isolated and identified as mouse p16INK4a and p15INK4b based on their homology to their human counterparts and their selective transcriptional induction by SV40T-..
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    The p16INK4a (alpha and beta form) and p15INK4b genes were analysed for homozygous deletion, hypermethylation and point mutation in B6C3F1 mouse lymphomas induced by 2',3'-dideoxycytidine or 1,3-butadiene...
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    ..Therefore, the reduction in PGCs in HP1gamma(-/-) embryos could be caused by impaired cell cycle in PGCs. These results suggest that HP1gamma plays an important role in keeping enough germ cells by regulating the PGC cell cycle. ..