KLF6 degradation after apoptotic DNA damage

Kruppel-like factor 6 (KLF6) is a cancer gene (www.sanger.ac.uk/genetics/CGP/Census/). Here, we demonstrate that KLF6 protein is rapidly degraded when apoptosis is induced via the intrinsic pathway by cisplatin, adriamycin, or UVB irradiation in multiple cell lines (HCT116, SW40, HepG2, PO-M, Skov3, NIH-3T3, 293T, GM09706, and MEF, IMR90). KLF6 degradation occurred in the presence or absence of p53, was associated with ubiquitination, mediated by the proteasome (half-life 16 min, unstimulated), and independent of caspases and calpain. KLF6 was unchanged by apoptosis via the extrinsic/death-receptor pathway. Deregulation of KLF6 stability may alter its tumor suppressor function and/or the response of tumors to chemotherapeutics. (c) 2006 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.