title: Role of c-Jun N-terminal kinase 1 (JNK1) in cell cycle checkpoint activated by the protease inhibitor N-acetyl-leucinyl-leucinyl-norleucinal.
abstract: The cysteine protease inhibitor N-acetyl-leucinyl-leucinyl-norleucinal (LLnL) inhibited the growth of the Calu-1 lung carcinoma cells and induced a prolonged cell cycle arrest in the S phase. c-Jun N-terminal kinases (JNKs) participate in cellular responses to mitogenic stimuli, environmental stresses, and apoptotic signals but its role in cell cycle checkpoint control has not been elucidated. In this report, we examined the role of JNK in LLnL-induced S phase checkpoint by overexpression of a dominant-negative mutant of JNK1 (JNK1-APF) in Calu-1 cells. Expression of high levels of JNK1-APF blocked the growth-inhibitory effects of LLnL and abrogated S phase arrest induced by LLnL. These results support the role of JNK in the activation of cell cycle checkpoint induced by LLnL.
authors.affiliation: Division of Hematology & Oncology, New York University Medical Center, NY 10016, USA.
authors.forename: W W
authors.initials: WW
authors.lastname: Tchou
authors.forename: T A
authors.initials: TA
authors.lastname: Yie
authors.forename: T H
authors.initials: TH
authors.lastname: Tan
authors.forename: W N
authors.initials: WN
authors.lastname: Rom
authors.forename: K M
authors.initials: KM
authors.lastname: Tchou-Wong
mesh_terms: D000841:Anisomycin / Q000494:pharmacology; D002453:Cell Cycle; D002460:Cell Line; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology*; D004789:Enzyme Activation; D048031:JNK Mitogen-Activated Protein Kinases; D007976:Leupeptins / Q000494:pharmacology*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D015853:Cysteine Proteinase Inhibitors; D007976:Leupeptins; C063261:acetylleucyl-leucyl-norleucinal; D000841:Anisomycin; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases