Role of c-Jun N-terminal kinase 1 (JNK1) in cell cycle checkpoint activated by the protease inhibitor N-acetyl-leucinyl-leucinyl-norleucinal

The cysteine protease inhibitor N-acetyl-leucinyl-leucinyl-norleucinal (LLn L) inhibited the growth of the Calu-1 lung carcinoma cells and induced a pr olonged cell cycle arrest in the S phase, c-Jun N-terminal kinases (JNKs) p articipate in cellular responses to mitogenic stimuli, environmental stress es, and apoptotic signals but its role in cell cycle checkpoint control has not been elucidated. In this report, me examined the role of JNK in LLnL-i nduced S phase checkpoint by overexpression of a dominant-negative mutant o f JNK1 (JNK1-APF) in Calu-1 cells. Expression of high levels of JNK1-APF bl ocked the growth-inhibitory effects of LLnL and abrogated S phase arrest in duced by LLnL. These results support the role of JNK in the activation of c ell cycle checkpoint induced by LLnL.