The p27Kip1 tumor suppressor gene: Still a suspect or proven guilty?
The p27Kip1 cyclin-dependent kinase inhibitor is considered to be a tumor suppressor even though somatic mutations in p27Kip1 are only rarely detected in human tumors. On the other hand, overwhelming evidence indicates that its hemizygous or posttranscriptional loss plays an important role in tumorigenesis. Based on these data, p27Kip1 was classified as a haploinsufficient tumor suppressor whose protein level has to be fine-tuned for optimal function. However, a recent study links germline mutations in p27Kip1 to multiple endocrine neoplasia syndrome in rats and humans, thus establishing p27Kip1 as a bona fide tumor suppressor gene.
Polyak
Kornelia
K
Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School and Brigham and Women's Hospital, 44 Binney Street, Boston, Massachusetts 02115, USA. kornelia_polyak@dfci.harvard.edu
D000818:Animals; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics* / Q000378:metabolism; D005260:Female; D016147:Genes, Tumor Suppressor; D006657:Histones / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D018761:Multiple Endocrine Neoplasia Type 1 / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D009369:Neoplasms / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D051381:Rats
D006657:Histones; C105373:MEN1 protein, human; D047428:Protein Kinase Inhibitors; D011518:Proto-Oncogene Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27