KLF6 degradation after apoptotic DNA damage.
Krüppel-like factor 6 (KLF6) is a cancer gene (). 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, PC3-M, Skov3, NIH-3T3, 293T, GM09706, and MEF, IMR-90). KLF6 degradation occurred in the presence or absence of p53, was associated with ubiquitination, mediated by the proteasome (half-life 16min, 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.
Banck
Michaela S
MS
Department of Medicine, Division of Hematology/Oncology, P.O. Box 1079, Mount Sinai School of Medicine, One Gustave Levy Place, Room 24-42A, New York, NY 10029, USA. michaela.banck@mssm.edu
Beaven
Simon W
SW
Narla
Goutham
G
Walsh
Martin J
MJ
Friedman
Scott L
SL
Beutler
Andreas S
AS
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D002945:Cisplatin / Q000494:pharmacology; D004249:DNA Damage; D006207:Half-Life; D006801:Humans; D000075723:Kruppel-Like Factor 6; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D061988:Proteasome Inhibitors; D011485:Protein Binding; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000494:pharmacology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D025801:Ubiquitin / Q000378:metabolism
C105465:KLF6 protein, human; C491358:Klf6 protein, mouse; D000075723:Kruppel-Like Factor 6; D051741:Kruppel-Like Transcription Factors; D061988:Proteasome Inhibitors; D011518:Proto-Oncogene Proteins; D053221:TNF-Related Apoptosis-Inducing Ligand; D014409:Tumor Necrosis Factor-alpha; D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex; D002945:Cisplatin