INK4 locus of the tumor-resistant rodent, the naked mole rat, expresses a functional p15/p16 hybrid isoform

Proceedings of the National Academy of Sciences of the United States of America

Volumn 112, Issue 4, 2015, Pages 1053-1058

  Tian, Xiao ^a   Azpurua, Jorge ^a,d   Ke, Zhonghe ^a   Augereau, Adeline ^b   Zhang, Zhengdong D ^c   Vijg, Jan ^c   Gladyshev, Vadim N ^b   Gorbunova, Vera ^a   Seluanov, Andrei ^a  

^a UNIVERSITY OF ROCHESTER   (United States)

^b BRIGHAM AND WOMEN S HOSPITAL   (United States)

^c ALBERT EINSTEIN COLLEGE OF MEDICINE   (United States)

^d UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT SAN ANTONIO   (United States)

Author keywords

INK4; Naked mole rat; p15; p16

Indexed keywords

CYCLIN DEPENDENT KINASE INHIBITOR; INHIBITORS OF CYCLIN DEPENTENT KINASE 4; PROTEIN P15; PROTEIN P16; TUMOR SUPPRESSOR PROTEIN; UNCLASSIFIED DRUG; CDKN2A PROTEIN, MOUSE; CDKN2B PROTEIN, HUMAN; CYCLIN DEPENDENT KINASE INHIBITOR 2A; CYCLIN DEPENDENT KINASE INHIBITOR 2B;

ALTERNATIVE RNA SPLICING; ANIMAL CELL; APOPTOSIS; ARTICLE; CELL AGING; CELL CULTURE; CELL CYCLE ARREST; CELL CYCLE REGULATION; CONTACT INHIBITION; EXON; FIBROBLAST; FLOW CYTOMETRY; GAMMA IRRADIATION; GENE EXPRESSION; GENE LOCUS; HUMAN; HUMAN CELL; MOUSE; NONHUMAN; NUCLEOTIDE SEQUENCE; ONCOGENE; PRIORITY JOURNAL; PROTEIN EXPRESSION; RAT; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; SKIN FIBROBLAST; TUMOR RESISTANCE; ULTRAVIOLET IRRADIATION; ANIMAL; BIOSYNTHESIS; CELL CYCLE CHECKPOINT; CELL LINE; CELL TRANSFORMATION; GENETICS; METABOLISM; MOLE RAT; PHYSIOLOGY; SPECIES DIFFERENCE;

HETEROCEPHALUS GLABER; RODENTIA;

ALTERNATIVE SPLICING; ANIMALS; CELL AGING; CELL CYCLE CHECKPOINTS; CELL LINE; CELL TRANSFORMATION, NEOPLASTIC; CYCLIN-DEPENDENT KINASE INHIBITOR P15; CYCLIN-DEPENDENT KINASE INHIBITOR P16; GENETIC LOCI; HUMANS; MICE; MOLE RATS; RATS; SPECIES SPECIFICITY;

EID: 84921742351     PISSN: 00278424     EISSN: 10916490     Source Type: Journal    
DOI: 10.1073/pnas.1418203112     Document Type: Article

References (46)

1. Edrey YH, Hanes M, Pinto M, Mele J, Buffenstein R (2011) Successful aging and sustained good health in the naked mole rat: A long-lived mammalian model for biogerontology and biomedical research. ILAR J 52(1):41-53.
2. Buffenstein R (2005) The naked mole-rat: A new long-living model for human aging research. J Gerontol A Biol Sci Med Sci 60(11):1369-1377.
3. Delaney MA, Nagy L, Kinsel MJ, Treuting PM (2013) Spontaneous histologic lesions of the adult naked mole rat (Heterocephalus glaber): A retrospective survey of lesions in a zoo population. Vet Pathol 50(4):607-621.
4. Buffenstein R (2008) Negligible senescence in the longest living rodent, the naked mole-rat: Insights from a successfully aging species. J Comp Physiol B 178(4):439-445.
5. Seluanov A, et al. (2009) Hypersensitivity to contact inhibition provides a clue to cancer resistance of naked mole-rat. Proc Natl Acad Sci USA 106(46):19352-19357.
6. Tian X, et al. (2013) High-molecular-mass hyaluronan mediates the cancer resistance of the naked mole rat. Nature 499(7458):346-349.
7. Kim WY, Sharpless NE (2006) The regulation of INK4/ARF in cancer and aging. Cell 127(2):265-275.
8. Serrano M, et al. (1996) Role of the INK4a locus in tumor suppression and cell mortality. Cell 85(1):27-37.
9. Sherr CJ (2012) Ink4-Arf locus in cancer and aging. Wiley Interdiscip Rev Dev Biol 1(5): 731-741.
10. Serrano M, Hannon GJ, Beach D (1993) A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4. Nature 366(6456):704-707.
11. Dai CY, Enders GH (2000) p16 INK4a can initiate an autonomous senescence program. Oncogene 19(13):1613-1622.
12. Brookes S, Rowe J, Gutierrez Del Arroyo A, Bond J, Peters G (2004) Contribution of p16(INK4a) to replicative senescence of human fibroblasts. Exp Cell Res 298(2):549-559.
13. Molofsky AV, et al. (2006) Increasing p16INK4a expression decreases forebrain progenitors and neurogenesis during ageing. Nature 443(7110):448-452.
14. Li H, et al. (2009) The Ink4/Arf locus is a barrier for iPS cell reprogramming. Nature 460(7259):1136-1139.
15. Tacutu R, Budovsky A, Yanai H, Fraifeld VE (2011) Molecular links between cellular senescence, longevity and age-related diseases: A systems biology perspective. Aging (Albany, NY Online) 3(12):1178-1191.
16. Ovadya Y, Krizhanovsky V (2014) Senescent cells: SASPected drivers of age-related pathologies. Biogerontology 15(6):627-642.
17. Liu Y, et al. (2009) Expression of p16(INK4a) in peripheral blood T-cells is a biomarker of human aging. Aging Cell 8(4):439-448.
18. Liu Y, et al. (2009) INK4/ARF transcript expression is associated with chromosome 9p21 variants linked to atherosclerosis. PLoS ONE 4(4):e5027.
19. Burd CE, et al. (2010) Expression of linear and novel circular forms of an INK4/ARF-associated non-coding RNA correlates with atherosclerosis risk. PLoS Genet 6(12): e1001233.
20. Kuo CL, et al. (2011) Cdkn2a is an atherosclerosis modifier locus that regulates monocyte/macrophage proliferation. Arterioscler Thromb Vasc Biol 31(11):2483-2492.
21. Yuan C, Selby TL, Li J, Byeon IJ, Tsai MD (2000) Tumor suppressor INK4: Refinement of p16INK4A structure and determination of p15INK4B structure by comparative modeling and NMR data. Protein Sci 9(6):1120-1128.
22. Yuan C, Li J, Selby TL, Byeon IJ, Tsai MD (1999) Tumor suppressor INK4: Comparisons of conformational properties between p16(INK4A) and p18(INK4C). J Mol Biol 294(1):201-211.
23. Kamijo T, et al. (1997) Tumor suppression at the mouse INK4a locus mediated by the alternative reading frame product p19ARF. Cell 91(5):649-659.
24. Zhang Y, Xiong Y, Yarbrough WG (1998) ARF promotes MDM2 degradation and stabilizes p53: ARF-INK4a locus deletion impairs both the Rb and p53 tumor suppression pathways. Cell 92(6):725-734.
25. Weber JD, et al. (2000) p53-independent functions of the p19(ARF) tumor suppressor. Genes Dev 14(18):2358-2365.
26. Szklarczyk R, Heringa J, Pond SK, Nekrutenko A (2007) Rapid asymmetric evolution of a dual-coding tumor suppressor INK4a/ARF locus contradicts its function. Proc Natl Acad Sci USA 104(31):12807-12812.
27. Gilley J, Fried M (2001) One INK4 gene and no ARF at the Fugu equivalent of the human INK4A/ARF/INK4B tumour suppressor locus. Oncogene 20(50):7447-7452.
28. Quelle DE, Zindy F, Ashmun RA, Sherr CJ (1995) Alternative reading frames of the INK4a tumor suppressor gene encode two unrelated proteins capable of inducing cell cycle arrest. Cell 83(6):993-1000.
29. Kim SH, Mitchell M, Fujii H, Llanos S, Peters G (2003) Absence of p16INK4a and truncation of ARF tumor suppressors in chickens. Proc Natl Acad Sci USA 100(1): 211-216.
30. Kim EB, et al. (2011) Genome sequencing reveals insights into physiology and longevity of the naked mole rat. Nature 479(7372):223-227.
31. Pavey S, Conroy S, Russell T, Gabrielli B (1999) Ultraviolet radiation induces p16CDKN2A expression in human skin. Cancer Res 59(17):4185-4189.
32. Krimpenfort P, Quon KC, Mooi WJ, Loonstra A, Berns A (2001) Loss of p16INK4a confers susceptibility to metastatic melanoma in mice. Nature 413(6851):83-86.
33. Schneider G, Schmid RM (2003) Genetic alterations in pancreatic carcinoma. Mol Cancer 2:15.
34. Esteller M, et al. (2001) K-ras and p16 aberrations confer poor prognosis in human colorectal cancer. J Clin Oncol 19(2):299-304.
35. Matheu A, et al. (2009) Anti-aging activity of the Ink4/Arf locus. Aging Cell 8(2): 152-161.
36. Matheu A, et al. (2004) Increased gene dosage of Ink4a/Arf results in cancer resistance and normal aging. Genes Dev 18(22):2736-2746.
37. Baker DJ, et al. (2011) Clearance of p16INK4a-positive senescent cells delays ageing-associated disorders. Nature 479(7372):232-236.
38. Jeck WR, Siebold AP, Sharpless NE (2012) Review: A meta-analysis of GWAS and age-associated diseases. Aging Cell 11(5):727-731.
39. Cocquet J, Chong A, Zhang G, Veitia RA (2006) Reverse transcriptase template switching and false alternative transcripts. Genomics 88(1):127-131.
40. Krimpenfort P, et al. (2007) p15INK4b is a critical tumour suppressor in the absence of p16INK4a. Nature 448(7156):943-946.
41. Zindy F, Quelle DE, Roussel MF, Sherr CJ (1997) Expression of the p16INK4a tumor suppressor versus other INK4 family members during mouse development and aging. Oncogene 15(2):203-211.
42. Krishnamurthy J, et al. (2004) Ink4a/Arf expression is a biomarker of aging. J Clin Invest 114(9):1299-1307.
43. Thullberg M, et al. (2000) Distinct versus redundant properties among members of the INK4 family of cyclin-dependent kinase inhibitors. FEBS Lett 470(2):161-166.
44. Leontieva OV, Demidenko ZN, Blagosklonny MV (2014) Contact inhibition and high cell density deactivate the mammalian target of rapamycin pathway, thus suppressing the senescence program. Proc Natl Acad Sci USA 111(24):8832-8837.
45. Tyner SD, et al. (2002) p53 mutant mice that display early ageing-associated phenotypes. Nature 415(6867):45-53.
46. Maier B, et al. (2004) Modulation of mammalian life span by the short isoform of p53. Genes Dev 18(3):306-319.