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multiple tumor suppressor-1 (MTS1); INK4; CDKN2A gene

Structure: - two different first exons 1-alpha & 1-beta spliced to the same 2nd & 3rd exons encode p16INK4A & p19ARF respectively, but p16INK4A & p19ARF show no homology at the amino acid level due to alternate reading frames - exon 1-beta codes for the protein region of p19ARF which binds MDM2 protein Pathology: - homozygously deleted at high frequency in cell lines derived from tumors of lung (non-small cell), breast, brain, bone, skin, bladder, kidney, ovary, pancreas [4], esophagus [4] & lymphocyte - deletion/mutation of MTS1 seen in melanoma cell lines

Related

malignant transformation suppression-1 (MTS1) gene; suppressor of anchorage independence-1 gene; transformation suppressor-1 (TFS-1) gene p16ink4A; cyclin-dependent kinase inhibitor 2A, isoforms 1/2/3; cyclin-dependent kinase 4 inhibitor A; CDK4I; p16-INK4a; p16INK4A; p16-INK4; multiple tumor suppressor 1; MTS-1; p16MTS1 (CDKN2A, CDKN2, MTS1)

General

tumor suppressor gene or anti-oncogene

Properties

TEMPLATE-FOR: messenger RNA TEMPLATE-FOR: cyclin-dependent kinase inhibitor 2A, isoform 4 LOCUS: human chromosome-9 P21 MOTIF: transcription factor binding site transcriptional start site exon intron transcriptional termination site

Database Correlations

OMIM 600160 MORBIDMAP 600160

References

  1. Kamb A, Gruis NA, Weaver-Feldhaus J, Liu Q, Harshman K, Tavtigian SV, Stockert E, Day RS 3rd, Johnson BE, Skolnick MH. A cell cycle regulator potentially involved in genesis of many tumor types. Science. 1994 Apr 15;264(5157):436-40. PMID: 8153634
  2. Quelle DE, Zindy F, Ashmun RA, Sherr CJ. Alternative reading frames of the INK4a tumor suppressor gene encode two unrelated proteins capable of inducing cell cycle arrest. Cell. 1995 Dec 15;83(6):993-1000. PMID: 8521522
  3. Zhang Y, Xiong Y, Yarbrough WG. ARF promotes MDM2 degradation and stabilizes p53: ARF-INK4a locus deletion impairs both the Rb and p53 tumor suppression pathways. Cell. 1998 Mar 20;92(6):725-34. PMID: 9529249
  4. Harrison's Principles of Internal Medicine, 14th ed. Fauci et al (eds), McGraw-Hill Inc. NY, 1998, pg 506