Complex structure and regulation of the P16 (MTS1) locus.

The p16 gene (P16, MTS1, CDKN2) encodes a negative regulator of the cell cycle. Molecular genetic techniques have been used to explore the role of p16 in normal development and cancer. Two transcripts derived from the p16 gene with distinct protein coding potentials are described. The previously undescribed transcript form has the same exons 2 and 3 as the p16-encoding mRNA but contains a different exon 1. The human p16 transcripts are detected in various tissues, and the ratio of the transcripts is regulated in both a tissue-specific and cell cycle-specific manner. The P16-derived mRNAs are probably generated from separate promoters, and transcription from one of the promoters appears to be regulated, at least in part, by the retinoblastoma gene product.

[1]  G. Hannon,et al.  A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4 , 1993, Nature.

[2]  C. Turck,et al.  Inhibition of CDK2 activity in vivo by an associated 20K regulatory subunit , 1993, Nature.

[3]  Ina Ruck,et al.  USA , 1969, The Lancet.

[4]  Tony Hunter,et al.  p27, a novel inhibitor of G1 cyclin-Cdk protein kinase activity, is related to p21 , 1994, Cell.

[5]  M. Kozak Point mutations define a sequence flanking the AUG initiator codon that modulates translation by eukaryotic ribosomes , 1986, Cell.

[6]  M. Skolnick,et al.  A cell cycle regulator potentially involved in genesis of many tumor types. , 1994, Science.

[7]  I. Herskowitz,et al.  Joining the complex: Cyclin-dependent kinase inhibitory proteins and the cell cycle , 1994, Cell.

[8]  D. Carson,et al.  Deletions of the cyclin-dependent kinase-4 inhibitor gene in multiple human cancers , 1994, Nature.

[9]  R. Weinberg,et al.  The retinoblastoma protein and the regulation of cell cycling. , 1992, Trends in biochemical sciences.

[10]  G. Peters,et al.  Lack of cyclin D‐Cdk complexes in Rb‐negative cells correlates with high levels of p16INK4/MTS1 tumour suppressor gene product. , 1995, The EMBO journal.

[11]  C. O'keefe,et al.  Growth suppression by p18, a p16INK4/MTS1- and p14INK4B/MTS2-related CDK6 inhibitor, correlates with wild-type pRb function. , 1994, Genes & development.

[12]  J. Trent,et al.  WAF1, a potential mediator of p53 tumor suppression , 1993, Cell.

[13]  A. Okamoto,et al.  Mutations and altered expression of p16INK4 in human cancer. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[14]  James M. Roberts,et al.  Cloning of p27 Kip1 , a cyclin-dependent kinase inhibitor and a potential mediator of extracellular antimitogenic signals , 1994, Cell.

[15]  C. Sherr G1 phase progression: Cycling on cue , 1994, Cell.

[16]  David Beach,et al.  p21 is a universal inhibitor of cyclin kinases , 1993, Nature.

[17]  S. Elledge,et al.  The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases , 1993, Cell.

[18]  R. Hruban,et al.  Frequent somatic mutations and homozygous deletions of the p16 (MTS1) gene in pancreatic adenocarcinoma , 1994, Nature Genetics.

[19]  J. Roberts,et al.  Inactivation of a Cdk2 inhibitor during interleukin 2-induced proliferation of human T lymphocytes , 1994, Molecular and cellular biology.

[20]  M H Skolnick,et al.  Localization of a putative tumor suppressor gene by using homozygous deletions in melanomas. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[21]  J. Massagué,et al.  Cyclic AMP-induced G1 phase arrest mediated by an inhibitor (p27 Kip1 ) of cyclin-dependent kinase 4 activation , 1994, Cell.

[22]  J. Sambrook,et al.  Molecular Cloning: A Laboratory Manual , 2001 .

[23]  J. Shay,et al.  Transcriptional repression of the D-type cyclin-dependent kinase inhibitor p16 by the retinoblastoma susceptibility gene product pRb. , 1994, Cancer research.

[24]  L. Bonetta,et al.  CDK6 (PLSTIRE) and CDK4 (PSK-J3) are a distinct subset of the cyclin-dependent kinases that associate with cyclin D1. , 1994, Oncogene.

[25]  S. Mori,et al.  Frequent somatic mutation of the MTS1/CDK4I (multiple tumor suppressor/cyclin-dependent kinase 4 inhibitor) gene in esophageal squamous cell carcinoma. , 1994, Cancer research.

[26]  W. Clark,et al.  Germline p16 mutations in familial melanoma , 1994, Nature Genetics.