Cdkn2a

Summary

Gene Symbol: Cdkn2a
Description: cyclin dependent kinase inhibitor 2A
Alias: ARF-INK4a, Arf, INK4a-ARF, Ink4a/Arf, MTS1, Pctr1, p16, p16(INK4a), p16INK4a, p19, p19ARF, cyclin-dependent kinase inhibitor 2A, CDK4I, alternative reading frame, cdkn2a, cyclin-dependent kinase 4 inhibitor A, cyclin-dependent kinase inhibitor 2A (p16, inhibits CDK4), cyclin-dependent kinase inhibitor 2A, isoforms 1/2, cyclin-dependent kinase inhibitor protein, mitochondrial smARF, p16-INK4, p16-INK4a
Species: mouse
Products:     Cdkn2a

Top Publications

  1. Herkert B, Dwertmann A, Herold S, Abed M, Naud J, Finkernagel F, et al. The Arf tumor suppressor protein inhibits Miz1 to suppress cell adhesion and induce apoptosis. J Cell Biol. 2010;188:905-18 pubmed publisher
    Oncogenic stress induces expression of the alternate reading frame (Arf) tumor suppressor protein. Arf then stabilizes p53, which leads to cell cycle arrest or apoptosis...
  2. Lacroix M, Caramel J, Goguet Rubio P, Linares L, Estrach S, Hatchi E, et al. Transcription factor E4F1 is essential for epidermal stem cell maintenance and skin homeostasis. Proc Natl Acad Sci U S A. 2010;107:21076-81 pubmed publisher
    ..The clonogenic potential of E4F1 KO ESCs is rescued by Bmi1 overexpression or by Ink4a/Arf or p53 depletion...
  3. Goel V, Ibrahim N, Jiang G, Singhal M, Fee S, Flotte T, et al. Melanocytic nevus-like hyperplasia and melanoma in transgenic BRAFV600E mice. Oncogene. 2009;28:2289-98 pubmed publisher
    ..Melanomas show CDKN2A loss, and genetic disruption of the CDKN2A locus greatly enhances melanoma formation, consistent with ..
  4. Woolfenden S, Zhu H, Charest A. A Cre/LoxP conditional luciferase reporter transgenic mouse for bioluminescence monitoring of tumorigenesis. Genesis. 2009;47:659-66 pubmed publisher
    ..Our results show that this reporter strain may be combined with various Cre/loxP mouse tumor models to allow for noninvasive longitudinal monitoring of tumor growth and therapeutic response in vivo. ..
  5. Chen H, Gu X, Su I, Bottino R, Contreras J, Tarakhovsky A, et al. Polycomb protein Ezh2 regulates pancreatic beta-cell Ink4a/Arf expression and regeneration in diabetes mellitus. Genes Dev. 2009;23:975-85 pubmed publisher
    ..Increased expression of the Ink4a/Arf locus, which encodes the cyclin-dependent kinase inhibitor p16(INK4a) and tumor suppressor p19(Arf), limits beta-..
  6. Yang J, Splittgerber R, Yull F, Kantrow S, Ayers G, Karin M, et al. Conditional ablation of Ikkb inhibits melanoma tumor development in mice. J Clin Invest. 2010;120:2563-74 pubmed publisher
    ..manner in mice null for the gene encoding the tumor suppressor inhibitor cyclin-dependent kinase 4/alternative reading frame (Ink4a/Arf)...
  7. Aguilera K, Rivera L, Hur H, Carbon J, Toombs J, Goldstein C, et al. Collagen signaling enhances tumor progression after anti-VEGF therapy in a murine model of pancreatic ductal adenocarcinoma. Cancer Res. 2014;74:1032-44 pubmed publisher
    ..Together, these findings suggest that collagen actively promotes PDA spread and that enhanced disease progression associated with anti-VEGF therapy can arise from elevated extracellular matrix-mediated signaling. ..
  8. Soudja S, Wehbe M, Mas A, Chasson L, de Tenbossche C, Huijbers I, et al. Tumor-initiated inflammation overrides protective adaptive immunity in an induced melanoma model in mice. Cancer Res. 2010;70:3515-25 pubmed publisher
    ..immune system on two differentially aggressive melanomas developing in mice on conditional deletion of the INK4A/ARF tumor suppressor gene, with concomitant expression of oncogene H-Ras(G12V) and a natural cancer-germline tumor ..
  9. Charles N, Ozawa T, Squatrito M, Bleau A, Brennan C, Hambardzumyan D, et al. Perivascular nitric oxide activates notch signaling and promotes stem-like character in PDGF-induced glioma cells. Cell Stem Cell. 2010;6:141-52 pubmed publisher
    ..This mechanism is conserved in human PDGFR amplified gliomas. The NO/cGMP/PKG pathway's promotion of stem cell-like character in the tumor PVN may identify therapeutic targets for this subset of gliomas. ..
  10. Lee J, Perera R, Wang H, Wu D, Liu X, Han S, et al. Stromal response to Hedgehog signaling restrains pancreatic cancer progression. Proc Natl Acad Sci U S A. 2014;111:E3091-100 pubmed publisher

Detail Information

Publications66

  1. Herkert B, Dwertmann A, Herold S, Abed M, Naud J, Finkernagel F, et al. The Arf tumor suppressor protein inhibits Miz1 to suppress cell adhesion and induce apoptosis. J Cell Biol. 2010;188:905-18 pubmed publisher
    Oncogenic stress induces expression of the alternate reading frame (Arf) tumor suppressor protein. Arf then stabilizes p53, which leads to cell cycle arrest or apoptosis...
  2. Lacroix M, Caramel J, Goguet Rubio P, Linares L, Estrach S, Hatchi E, et al. Transcription factor E4F1 is essential for epidermal stem cell maintenance and skin homeostasis. Proc Natl Acad Sci U S A. 2010;107:21076-81 pubmed publisher
    ..The clonogenic potential of E4F1 KO ESCs is rescued by Bmi1 overexpression or by Ink4a/Arf or p53 depletion...
  3. Goel V, Ibrahim N, Jiang G, Singhal M, Fee S, Flotte T, et al. Melanocytic nevus-like hyperplasia and melanoma in transgenic BRAFV600E mice. Oncogene. 2009;28:2289-98 pubmed publisher
    ..Melanomas show CDKN2A loss, and genetic disruption of the CDKN2A locus greatly enhances melanoma formation, consistent with ..
  4. Woolfenden S, Zhu H, Charest A. A Cre/LoxP conditional luciferase reporter transgenic mouse for bioluminescence monitoring of tumorigenesis. Genesis. 2009;47:659-66 pubmed publisher
    ..Our results show that this reporter strain may be combined with various Cre/loxP mouse tumor models to allow for noninvasive longitudinal monitoring of tumor growth and therapeutic response in vivo. ..
  5. Chen H, Gu X, Su I, Bottino R, Contreras J, Tarakhovsky A, et al. Polycomb protein Ezh2 regulates pancreatic beta-cell Ink4a/Arf expression and regeneration in diabetes mellitus. Genes Dev. 2009;23:975-85 pubmed publisher
    ..Increased expression of the Ink4a/Arf locus, which encodes the cyclin-dependent kinase inhibitor p16(INK4a) and tumor suppressor p19(Arf), limits beta-..
  6. Yang J, Splittgerber R, Yull F, Kantrow S, Ayers G, Karin M, et al. Conditional ablation of Ikkb inhibits melanoma tumor development in mice. J Clin Invest. 2010;120:2563-74 pubmed publisher
    ..manner in mice null for the gene encoding the tumor suppressor inhibitor cyclin-dependent kinase 4/alternative reading frame (Ink4a/Arf)...
  7. Aguilera K, Rivera L, Hur H, Carbon J, Toombs J, Goldstein C, et al. Collagen signaling enhances tumor progression after anti-VEGF therapy in a murine model of pancreatic ductal adenocarcinoma. Cancer Res. 2014;74:1032-44 pubmed publisher
    ..Together, these findings suggest that collagen actively promotes PDA spread and that enhanced disease progression associated with anti-VEGF therapy can arise from elevated extracellular matrix-mediated signaling. ..
  8. Soudja S, Wehbe M, Mas A, Chasson L, de Tenbossche C, Huijbers I, et al. Tumor-initiated inflammation overrides protective adaptive immunity in an induced melanoma model in mice. Cancer Res. 2010;70:3515-25 pubmed publisher
    ..immune system on two differentially aggressive melanomas developing in mice on conditional deletion of the INK4A/ARF tumor suppressor gene, with concomitant expression of oncogene H-Ras(G12V) and a natural cancer-germline tumor ..
  9. Charles N, Ozawa T, Squatrito M, Bleau A, Brennan C, Hambardzumyan D, et al. Perivascular nitric oxide activates notch signaling and promotes stem-like character in PDGF-induced glioma cells. Cell Stem Cell. 2010;6:141-52 pubmed publisher
    ..This mechanism is conserved in human PDGFR amplified gliomas. The NO/cGMP/PKG pathway's promotion of stem cell-like character in the tumor PVN may identify therapeutic targets for this subset of gliomas. ..
  10. Lee J, Perera R, Wang H, Wu D, Liu X, Han S, et al. Stromal response to Hedgehog signaling restrains pancreatic cancer progression. Proc Natl Acad Sci U S A. 2014;111:E3091-100 pubmed publisher
  11. Guerra C, Collado M, Navas C, Schuhmacher A, Hernández Porras I, Canamero M, et al. Pancreatitis-induced inflammation contributes to pancreatic cancer by inhibiting oncogene-induced senescence. Cancer Cell. 2011;19:728-39 pubmed publisher
    ..transformation by some of the most robust oncogenic insults including expression of K-Ras oncogenes and loss of p16Ink4a/p19Arf or Trp53 tumor suppressors...
  12. Miceli A, Saporita A, Weber J. Hypergrowth mTORC1 signals translationally activate the ARF tumor suppressor checkpoint. Mol Cell Biol. 2012;32:348-64 pubmed publisher
    The ARF tumor suppressor is a potent sensor of hyperproliferative cues emanating from oncogenic signaling. ARF responds to these cues by eliciting a cell cycle arrest, effectively abating the tumorigenic potential of these stimuli...
  13. Dhomen N, Reis Filho J, da Rocha Dias S, Hayward R, Savage K, Delmas V, et al. Oncogenic Braf induces melanocyte senescence and melanoma in mice. Cancer Cell. 2009;15:294-303 pubmed publisher
    ..We show that the tumor suppressor p16(INK4a) is not required to induce melanocyte senescence and that its loss is not required for tumor progression, ..
  14. Navas C, Hernández Porras I, Schuhmacher A, Sibilia M, Guerra C, Barbacid M. EGF receptor signaling is essential for k-ras oncogene-driven pancreatic ductal adenocarcinoma. Cancer Cell. 2012;22:318-30 pubmed publisher
    ..EGFRs were also essential even in the context of pancreatic injury and absence of p16Ink4a/p19Arf. Only loss of p53 made pancreatic tumors independent of EGFR signaling...
  15. Kuo C, Murphy A, Sayers S, Li R, Yvan Charvet L, Davis J, et al. Cdkn2a is an atherosclerosis modifier locus that regulates monocyte/macrophage proliferation. Arterioscler Thromb Vasc Biol. 2011;31:2483-92 pubmed publisher
    Common genetic variants in a 58-kb region of chromosome 9p21, near the CDKN2A/CDKN2B tumor suppressor locus, are strongly associated with coronary artery disease. However, the underlying mechanism of action remains unknown...
  16. Collier L, Adams D, Hackett C, Bendzick L, Akagi K, Davies M, et al. Whole-body sleeping beauty mutagenesis can cause penetrant leukemia/lymphoma and rare high-grade glioma without associated embryonic lethality. Cancer Res. 2009;69:8429-37 pubmed publisher
    ..Furthermore, the SB system could be used to identify new genes involved in lymphomagenesis/leukemogenesis. ..
  17. Fomchenko E, Dougherty J, Helmy K, Katz A, Pietras A, Brennan C, et al. Recruited cells can become transformed and overtake PDGF-induced murine gliomas in vivo during tumor progression. PLoS ONE. 2011;6:e20605 pubmed publisher
    ..progression is associated with elevated growth factor signaling and loss of function of tumor suppressors Ink4a, Arf and Pten. Yet, gliomas are cellularly heterogeneous; they recruit and trap normal cells during infiltration...
  18. Singh A, Greninger P, Rhodes D, Koopman L, Violette S, Bardeesy N, et al. A gene expression signature associated with "K-Ras addiction" reveals regulators of EMT and tumor cell survival. Cancer Cell. 2009;15:489-500 pubmed publisher
    ..These findings indicate that epithelial differentiation and tumor cell viability are associated, and that EMT regulators in "K-Ras-addicted" cancers represent candidate therapeutic targets. ..
  19. Chiba T, Seki A, Aoki R, Ichikawa H, Negishi M, Miyagi S, et al. Bmi1 promotes hepatic stem cell expansion and tumorigenicity in both Ink4a/Arf-dependent and -independent manners in mice. Hepatology. 2010;52:1111-23 pubmed publisher
    ..In the present study, we examined the contribution of the Ink4a/Arf tumor suppressor gene locus, one of the major targets of Bmi1, to stem cell expansion and cancer initiation...
  20. Gonzalez Navarro H, Abu Nabah Y, Vinue A, Andrés Manzano M, Collado M, Serrano M, et al. p19(ARF) deficiency reduces macrophage and vascular smooth muscle cell apoptosis and aggravates atherosclerosis. J Am Coll Cardiol. 2010;55:2258-68 pubmed publisher
    ..the role in atherosclerosis of the tumor suppressor protein ARF (human p14(ARF), mouse p19(ARF)) encoded by the CDKN2A gene...
  21. Mallen St Clair J, Soydaner Azeloglu R, Lee K, Taylor L, Livanos A, Pylayeva Gupta Y, et al. EZH2 couples pancreatic regeneration to neoplastic progression. Genes Dev. 2012;26:439-44 pubmed publisher
  22. Su X, Cho M, Gi Y, Ayanga B, Sherr C, Flores E. Rescue of key features of the p63-null epithelial phenotype by inactivation of Ink4a and Arf. EMBO J. 2009;28:1904-15 pubmed publisher
    ..Here, we show that inactivation of p63 in mice is accompanied by aberrantly increased expression of the Ink4a and Arf tumour suppressor genes...
  23. Kawagishi H, Nakamura H, Maruyama M, Mizutani S, Sugimoto K, Takagi M, et al. ARF suppresses tumor angiogenesis through translational control of VEGFA mRNA. Cancer Res. 2010;70:4749-58 pubmed publisher
    ..Here, we report that the nucleolar tumor suppressor p19(ARF) suppresses VEGFA expression, acting at the level of mRNA translation without affecting the transcription of the ..
  24. Zhang H, Ding J, Jin J, Guo J, Liu J, Karaplis A, et al. Defects in mesenchymal stem cell self-renewal and cell fate determination lead to an osteopenic phenotype in Bmi-1 null mice. J Bone Miner Res. 2010;25:640-52 pubmed publisher
    ..apoptosis of BM-MSCs were associated with upregulation of senescence-associated tumor-suppressor genes, including p16, p19, and p27...
  25. Dhawan S, Tschen S, Bhushan A. Bmi-1 regulates the Ink4a/Arf locus to control pancreatic beta-cell proliferation. Genes Dev. 2009;23:906-11 pubmed publisher
    ..We report that in aged islets, derepression of the Ink4a/Arf locus is associated with decreased Bmi-1 binding, loss of H2A ubiquitylation, increased MLL1 recruitment, and a ..
  26. Carragher L, Snell K, Giblett S, Aldridge V, Patel B, Cook S, et al. V600EBraf induces gastrointestinal crypt senescence and promotes tumour progression through enhanced CpG methylation of p16INK4a. EMBO Mol Med. 2010;2:458-71 pubmed publisher
    ..is associated with down-regulation of p16(Ink4a) through enhanced CpG methylation of exon 1 and knockout of Cdkn2a confirms this gene is a barrier to tumour progression...
  27. Macias E, Jin A, Deisenroth C, Bhat K, Mao H, Lindström M, et al. An ARF-independent c-MYC-activated tumor suppression pathway mediated by ribosomal protein-Mdm2 Interaction. Cancer Cell. 2010;18:231-43 pubmed publisher
    ..Furthermore, ribosomal perturbation-induced p53 response does not require tumor suppressor p19ARF. Collectively, our findings establish RP-Mdm2 interaction as a genuine p53 stress-signaling pathway activated by ..
  28. Sousa Victor P, Gutarra S, García Prat L, Rodriguez Ubreva J, Ortet L, Ruiz Bonilla V, et al. Geriatric muscle stem cells switch reversible quiescence into senescence. Nature. 2014;506:316-21 pubmed publisher
    ..quiescence by switching to an irreversible pre-senescence state, caused by derepression of p16(INK4a) (also called Cdkn2a)...
  29. Cudejko C, Wouters K, Fuentes L, Hannou S, Paquet C, Bantubungi K, et al. p16INK4a deficiency promotes IL-4-induced polarization and inhibits proinflammatory signaling in macrophages. Blood. 2011;118:2556-66 pubmed publisher
    The CDKN2A locus, which contains the tumor suppressor gene p16(INK4a), is associated with an increased risk of age-related inflammatory diseases, such as cardiovascular disease and type 2 diabetes, in which macrophages play a crucial role...
  30. Cardenas J, Owens A, Krishnamurthy J, Sharpless N, Whinna H, Church F. Overexpression of the cell cycle inhibitor p16INK4a promotes a prothrombotic phenotype following vascular injury in mice. Arterioscler Thromb Vasc Biol. 2011;31:827-33 pubmed publisher
    Age-associated cellular senescence is thought to promote vascular dysfunction. p16(INK4a) is a cell cycle inhibitor that promotes senescence and is upregulated during normal aging...
  31. Saporita A, Chang H, Winkeler C, Apicelli A, Kladney R, Wang J, et al. RNA helicase DDX5 is a p53-independent target of ARF that participates in ribosome biogenesis. Cancer Res. 2011;71:6708-17 pubmed publisher
    The p19ARF tumor suppressor limits ribosome biogenesis and responds to hyperproliferative signals to activate the p53 checkpoint response...
  32. Gromley A, Churchman M, Zindy F, Sherr C. Transient expression of the Arf tumor suppressor during male germ cell and eye development in Arf-Cre reporter mice. Proc Natl Acad Sci U S A. 2009;106:6285-90 pubmed publisher
    The Arf tumor suppressor is expressed transiently during mouse male germ cell and eye development...
  33. Burd C, Sorrentino J, Clark K, Darr D, Krishnamurthy J, Deal A, et al. Monitoring tumorigenesis and senescence in vivo with a p16(INK4a)-luciferase model. Cell. 2013;152:340-51 pubmed publisher
    ..Monitoring cancer and aging in vivo remains experimentally challenging. Here, we describe a luciferase knockin mouse (p16(LUC)), which faithfully reports expression of p16(INK4a), a tumor suppressor and aging biomarker...
  34. Dominguez Brauer C, Chen Y, Brauer P, Pimkina J, Raychaudhuri P. ARF stimulates XPC to trigger nucleotide excision repair by regulating the repressor complex of E2F4. EMBO Rep. 2009;10:1036-42 pubmed publisher
    The tumour suppressor ARF (alternative reading frame), which is mutated or silenced in various tumours, has a crucial role in tumour surveillance to suppress unwarranted cell growth and proliferation...
  35. Agherbi H, Gaussmann Wenger A, Verthuy C, Chasson L, Serrano M, Djabali M. Polycomb mediated epigenetic silencing and replication timing at the INK4a/ARF locus during senescence. PLoS ONE. 2009;4:e5622 pubmed publisher
    The INK4/ARF locus encodes three tumor suppressor genes (p15(Ink4b), Arf and p16(Ink4a)) and is frequently inactivated in a large number of human cancers. Mechanisms regulating INK4/ARF expression are not fully characterized...
  36. Bender A, Collier L, Rodriguez F, Tieu C, Larson J, Halder C, et al. Sleeping beauty-mediated somatic mutagenesis implicates CSF1 in the formation of high-grade astrocytomas. Cancer Res. 2010;70:3557-65 pubmed publisher
    ..Together, these results indicate that SB-insertional mutagenesis can identify high-grade astrocytoma-associated genes and they imply an important role for CSF1 in the development of these tumors. ..
  37. Jenkins N, Liu T, Cassidy P, Leachman S, Boucher K, Goodson A, et al. The p16(INK4A) tumor suppressor regulates cellular oxidative stress. Oncogene. 2011;30:265-74 pubmed publisher
    ..ROS levels were also observed in p16-depleted human keratinocytes and in whole skin and dermal fibroblasts from Cdkn2a-deficient mice...
  38. Lessard F, Morin F, Ivanchuk S, Langlois F, Stefanovsky V, Rutka J, et al. The ARF tumor suppressor controls ribosome biogenesis by regulating the RNA polymerase I transcription factor TTF-I. Mol Cell. 2010;38:539-50 pubmed publisher
    The p14/p19(ARF) (ARF) product of the CDKN2A gene displays tumor suppressor activity both in the presence and absence of p53/TP53...
  39. Genovese G, Ergun A, Shukla S, Campos B, Hanna J, Ghosh P, et al. microRNA regulatory network inference identifies miR-34a as a novel regulator of TGF-? signaling in glioblastoma. Cancer Discov. 2012;2:736-49 pubmed
    ..Specifically in glioblastoma, within the context of the global network, promoter enrichment analysis of network edges uncovered a novel regulation of TGF-? signaling via a Smad4 transcriptomic network by miR-34a. ..
  40. Hettmer S, Liu J, Miller C, Lindsay M, Sparks C, Guertin D, et al. Sarcomas induced in discrete subsets of prospectively isolated skeletal muscle cells. Proc Natl Acad Sci U S A. 2011;108:20002-7 pubmed publisher
    ..of Kirsten rat sarcoma viral oncogene [Kras(G12V)] and disruption of cyclin-dependent kinase inhibitor 2A (CDKN2A; p16p19) in prospectively isolated satellite cells gave rise to pleomorphic rhabdomyosarcomas (MyoD-, Myogenin- ..
  41. Vincent D, Yan K, Treilleux I, Gay F, Arfi V, Kaniewski B, et al. Inactivation of TIF1gamma cooperates with Kras to induce cystic tumors of the pancreas. PLoS Genet. 2009;5:e1000575 pubmed publisher
  42. Agger K, Cloos P, Rudkjaer L, Williams K, Andersen G, Christensen J, et al. The H3K27me3 demethylase JMJD3 contributes to the activation of the INK4A-ARF locus in response to oncogene- and stress-induced senescence. Genes Dev. 2009;23:1171-6 pubmed publisher
    The tumor suppressor proteins p16INK4A and p14ARF, encoded by the INK4A-ARF locus, are key regulators of cellular senescence...
  43. Treanor L, Volanakis E, Zhou S, Lu T, Sherr C, Sorrentino B. Functional interactions between Lmo2, the Arf tumor suppressor, and Notch1 in murine T-cell malignancies. Blood. 2011;117:5453-62 pubmed publisher
    ..genetic events in LMO2-associated T-cell acute lymphoblastic leukemia (T-ALL), we investigated the roles of Arf tumor suppressor loss and Notch activation in murine models of transplantation...
  44. Lindberg N, Jiang Y, Xie Y, Bolouri H, Kastemar M, Olofsson T, et al. Oncogenic signaling is dominant to cell of origin and dictates astrocytic or oligodendroglial tumor development from oligodendrocyte precursor cells. J Neurosci. 2014;34:14644-51 pubmed publisher
    ..them to oligodendroglial platelet-derived growth factor B-induced tumors in Ctv-a mice with targeted deletions of Cdkn2a (p16(Ink4a-/-), p19(Arf-/-), Cdkn2a(-/-))...
  45. Oguro H, Yuan J, Ichikawa H, Ikawa T, Yamazaki S, Kawamoto H, et al. Poised lineage specification in multipotential hematopoietic stem and progenitor cells by the polycomb protein Bmi1. Cell Stem Cell. 2010;6:279-86 pubmed publisher
    ..Thus, Bmi1 is required to reinforce bivalent domains at key developmental regulator gene loci to maintain lineage specification poised for activation in adult stem cells. ..
  46. Morton J, Timpson P, Karim S, Ridgway R, Athineos D, Doyle B, et al. Mutant p53 drives metastasis and overcomes growth arrest/senescence in pancreatic cancer. Proc Natl Acad Sci U S A. 2010;107:246-51 pubmed publisher
  47. Hidalgo I, Herrera Merchan A, Ligos J, Carramolino L, Nunez J, Martinez F, et al. Ezh1 is required for hematopoietic stem cell maintenance and prevents senescence-like cell cycle arrest. Cell Stem Cell. 2012;11:649-62 pubmed publisher
    ..Deletion of Cdkn2a on the Ezh1 null background rescued HSC proliferation and survival...
  48. Ozawa T, Riester M, Cheng Y, Huse J, Squatrito M, Helmy K, et al. Most human non-GCIMP glioblastoma subtypes evolve from a common proneural-like precursor glioma. Cancer Cell. 2014;26:288-300 pubmed publisher
    ..The most common order of evolutionary events is 1) chromosome (chr) 7 gain and chr10 loss, followed by 2) CDKN2A loss and/or TP53 mutation, and 3) alterations canonical for specific subtypes...
  49. Dineen S, Roland C, Greer R, Carbon J, Toombs J, Gupta P, et al. Smac mimetic increases chemotherapy response and improves survival in mice with pancreatic cancer. Cancer Res. 2010;70:2852-61 pubmed publisher
    ..The continued development of JP1201 and other strategies designed to enhance therapy-induced apoptosis in pancreatic cancer is warranted...
  50. Grange M, Buferne M, Verdeil G, Leserman L, Schmitt Verhulst A, Auphan Anezin N. Activated STAT5 promotes long-lived cytotoxic CD8+ T cells that induce regression of autochthonous melanoma. Cancer Res. 2012;72:76-87 pubmed publisher
  51. Di Tommaso A, Hagen J, Tompkins V, Muniz V, Dudakovic A, Kitzis A, et al. Residues in the alternative reading frame tumor suppressor that influence its stability and p53-independent activities. Exp Cell Res. 2009;315:1326-35 pubmed publisher
    The Alternative Reading Frame (ARF) protein suppresses tumorigenesis through p53-dependent and p53-independent pathways. Most of ARF's anti-proliferative activity is conferred by sequences in its first exon...
  52. Baker D, Wijshake T, Tchkonia T, Lebrasseur N, Childs B, van De Sluis B, et al. Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders. Nature. 2011;479:232-6 pubmed publisher
    ..To address these fundamental questions, we made use of a biomarker for senescence, p16(Ink4a), to design a novel transgene, INK-ATTAC, for inducible elimination of p16(Ink4a)-positive senescent cells ..
  53. Al Khalaf H, Colak D, Al Saif M, Al Bakheet A, Hendrayani S, Al Yousef N, et al. p16( INK4a) positively regulates cyclin D1 and E2F1 through negative control of AUF1. PLoS ONE. 2011;6:e21111 pubmed publisher
    The cyclin-D/CDK4,6/p16(INK4a)/pRB/E2F pathway, a key regulator of the critical G1 to S phase transition of the cell cycle, is universally disrupted in human cancer...
  54. Chen Z, Carracedo A, Lin H, Koutcher J, Behrendt N, Egia A, et al. Differential p53-independent outcomes of p19(Arf) loss in oncogenesis. Sci Signal. 2009;2:ra44 pubmed publisher
    One reported function of the tumor suppressor p19(Arf) is to stabilize p53, providing a critical checkpoint in the response to oncogenic insults...
  55. Premsrirut P, Dow L, Kim S, Camiolo M, Malone C, Miething C, et al. A rapid and scalable system for studying gene function in mice using conditional RNA interference. Cell. 2011;145:145-58 pubmed publisher
    ..tet-regulated shRNA transgenic lines targeting Firefly and Renilla luciferases, Oct4 and tumor suppressors p53, p16(INK4a), p19(ARF) and APC and demonstrate potent gene silencing and GFP-tracked knockdown in a broad range of ..
  56. Yamakoshi K, Takahashi A, Hirota F, Nakayama R, Ishimaru N, Kubo Y, et al. Real-time in vivo imaging of p16Ink4a reveals cross talk with p53. J Cell Biol. 2009;186:393-407 pubmed publisher
    Expression of the p16(Ink4a) tumor suppressor gene, a sensor of oncogenic stress, is up-regulated by a variety of potentially oncogenic stimuli in cultured primary cells...
  57. 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
    ..5 dpc, but in its absence, upregulation of other cell cycle suppressors, including Cdkn1b and Cdkn2b, can induce delayed germ cell arrest. ..
  58. Bennecke M, Kriegl L, Bajbouj M, Retzlaff K, Robine S, Jung A, et al. Ink4a/Arf and oncogene-induced senescence prevent tumor progression during alternative colorectal tumorigenesis. Cancer Cell. 2010;18:135-46 pubmed publisher
    ..cell specific expression of oncogenic K-ras(G12D) in mice induces serrated hyperplasia, which is characterized by p16(ink4a) overexpression and induction of senescence...
  59. Bruggeman S, Hulsman D, Tanger E, Buckle T, Blom M, Zevenhoven J, et al. Bmi1 controls tumor development in an Ink4a/Arf-independent manner in a mouse model for glioma. Cancer Cell. 2007;12:328-41 pubmed
    ..Repression of the Ink4a/Arf locus is a well described mechanism through which Bmi1 can exert its proliferative effects...
  60. Chin L, Pomerantz J, Polsky D, Jacobson M, Cohen C, Cordon Cardo C, et al. Cooperative effects of INK4a and ras in melanoma susceptibility in vivo. Genes Dev. 1997;11:2822-34 pubmed
    The familial melanoma gene (INK4a/MTS1/CDKN2) encodes potent tumor suppressor activity. Although mice null for the ink4a homolog develop a cancer-prone condition, a pathogenetic link to melanoma susceptibility has yet to be established...
  61. 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
    ..Transcripts encoding the INK4a alternative reading frame product p19ARF were not detected before birth but were ubiquitous postnatally...
  62. Murphy D, Junttila M, Pouyet L, Karnezis A, Shchors K, Bui D, et al. Distinct thresholds govern Myc's biological output in vivo. Cancer Cell. 2008;14:447-57 pubmed publisher
    ..are competent to drive ectopic proliferation of somatic cells and oncogenesis, but activation of the apoptotic and ARF/p53 intrinsic tumor surveillance pathways requires Myc overexpression...
  63. Tuveson D, Hingorani S. Ductal pancreatic cancer in humans and mice. Cold Spring Harb Symp Quant Biol. 2005;70:65-72 pubmed
    ..In addition, lessons from modeling PDA may be applicable to other tumor types and illuminate general principles of carcinogenesis. ..
  64. Uhrbom L, Dai C, Celestino J, Rosenblum M, Fuller G, Holland E. Ink4a-Arf loss cooperates with KRas activation in astrocytes and neural progenitors to generate glioblastomas of various morphologies depending on activated Akt. Cancer Res. 2002;62:5551-8 pubmed
    Deletion of the INK4a-ARF locus is found in the majority of human malignant gliomas. However, the role of INK4a-ARF loss in gliomagenesis is unclear...
  65. Terzian T, Suh Y, Iwakuma T, Post S, Neumann M, Lang G, et al. The inherent instability of mutant p53 is alleviated by Mdm2 or p16INK4a loss. Genes Dev. 2008;22:1337-44 pubmed publisher
    ..the regulation of mutant p53 stability by Mdm2, an E3 ubiquitin ligase that targets p53 for degradation, and p16INK4a, a member of the Rb tumor suppressor pathway...