How to decrease p27Kip1 levels during tumor development.
p27Kip1, a cyclin-cdk inhibitor, is a tumor suppressor. An overwhelming amount of data correlate p27 abundance to tumor prognosis in humans. Mouse models have supported the importance of decreasing p27 to tumor incidence. Inactivation of most tumor suppressors occurs at the level of gene mutation or silencing, but p27 is regulated posttranscriptionally, and how its level is reduced in cancer is largely unknown. Reports on a series of allelic mice with p27 mutations affecting different posttranscriptional regulatory pathways are emerging and being used to examine which pathways are necessary for p27 turnover associated with tumor development, with surprising results.
Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, New York 10021, USA. a-koff@ski.mskcc.org
Andrew
A
Koff
D000818:Animals; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology*; D044786:S-Phase Kinase-Associated Proteins / Q000378:metabolism
D044786:S-Phase Kinase-Associated Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27