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Functional Interaction between the Transcription Factor Krüppel-like Factor 5 and Poly(ADP-ribose) Polymerase-1 in Cardiovascular Apoptosis

2007; Elsevier BV; Volume: 282; Issue: 13 Linguagem: Inglês

10.1074/jbc.m608098200

1083-351X

Toru Suzuki, Toshiya Nishi, Tomoko Nagino, Kana Sasaki, Kenichi Aizawa, Nanae Kada, Daigo Sawaki, Yoshiko Munemasa, Takayoshi Matsumura, Shinsuke Muto, Masataka Sata, Kiyoshi Miyagawa, Masami Horikoshi, Ryozo Nagai,

Cancer-related gene regulation

Krüppel-like factor 5 (KLF5) is a transcription factor important in regulation of the cardiovascular response to external stress. KLF5 regulates pathological cell growth, and its acetylation is important for this effect. Its mechanisms of action, however, are still unclear. Analysis in KLF5-deficient mice showed that KLF5 confers apoptotic resistance in vascular lesions. Mechanistic analysis further showed that it specifically interacts with poly(ADP-ribose) polymerase-1 (PARP-1), a nuclear enzyme important in DNA repair and apoptosis. KLF5 interacted with a proteolytic fragment of PARP-1, and acetylation of KLF5 under apoptotic conditions increased their affinity. Moreover, KLF5 wild-type (but not a non-acetylatable point mutant) inhibited apoptosis as induced by the PARP-1 fragment. Collectively, we have found that KLF5 regulates apoptosis and targets PARP-1, and further, for acetylation to regulate these effects. Our findings thus implicate functional interaction between the transcription factor KLF5 and PARP-1 in cardiovascular apoptosis.