This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Gump, J. Articles by Koh, J. Search for Related Content PubMed PubMed Citation Articles by Gump, J. Articles by Koh, J.

The COOH Terminus of p18INK4C Distinguishes Function from p16INK4A¹

Departments of Molecular Physiology and Biophysics [J. G.], Pathology [S. T., J. K.], and Medicine [J. K.], University of Vermont, Burlington, Vermont 05405

The INK4 family of proteins consists of four members which can block progression from the G₁-to-S phase of the cell cycle by inhibiting the activity of cyclin dependent kinases (cdks) 4 and 6. Although the gene encoding p16^INK4a is commonly inactivated in human tumors, p18^INK4c is rarely altered. We show here that overexpression of p18^INK4c does not block cell cycle progression in a T-cell acute lymphocytic leukemia cell line (CEM) sensitive to p16^INK4a-mediated G₁ arrest. A chimera consisting of the kinase-binding region of p16^INK4a fused to the COOH terminus of p18^INK4c is active in all known biochemical assays for INK4 function, but it does not arrest CEM cells. These data imply a novel level of p18^INK4c regulation mediated through the COOH terminus and suggest that functional differences might underlie the distinct mutational profiles observed for p16^INK4a and p18^INK4c in tumors.