D-type cyclins, in association with the cyclin-dependent kinases Cdk4 or Cdk6, promote progression through the G1 phase of the cell cycle by phosphorylating the retinoblastoma protein (RB). The activities of Cdk4 and Cdk6 are constrained by inhibitors such as p16, the product of the CDKN2 gene on human chromosome 9p21 (refs 12-14). The frequent deletion or mutation of CDKN2 in tumour cells suggests that p16 acts as a tumour suppressor. We show that wild-type p16 arrests normal diploid cells in late G1, whereas a tumour-associated mutant of p16 does not. Significantly, the ability of p16 to induce cell-cycle arrest is lost in cells lacking functional RB, including primary fibroblasts from Rb-/- mouse embryos. Thus, loss of p16, overexpression of D-cyclins and loss of RB have similar effects on G1 progression, and may represent a common pathway to tumorigenesis.

• MeSH
• buněčný cyklus * fyziologie   MeSH
• cyklin D1 MeSH
• cyklin-dependentní kinasa 4 MeSH
• cyklin-dependentní kinasa 6 MeSH
• cyklin-dependentní kinasy * MeSH
• cykliny fyziologie   MeSH
• Escherichia coli MeSH
• G1 fáze fyziologie   MeSH
• inhibitor p16 cyklin-dependentní kinasy MeSH
• klonování DNA MeSH
• kultivované buňky MeSH
• lidé MeSH
• mikroinjekce MeSH
• mutace MeSH
• myši inbrední BALB C MeSH
• myši MeSH
• nádorové buňky kultivované MeSH
• onkogenní proteiny fyziologie   MeSH
• protein-serin-threoninkinasy antagonisté a inhibitory   MeSH
• protoonkogenní proteiny * MeSH
• rekombinantní proteiny metabolismus   MeSH
• retinoblastomový protein * fyziologie   MeSH
• transportní proteiny fyziologie   genetika   MeSH
• tumor supresorové geny * MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH