title: Functional interaction between the transcription factor Krüppel-like factor 5 and poly(ADP-ribose) polymerase-1 in cardiovascular apoptosis.
abstract: 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.
authors.affiliation: Department of Cardiovascular Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan; Department of Clinical Bioinformatics, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. Electronic address: torusuzu-tky@umin.ac.jp.
authors.forename: Toru
authors.initials: T
authors.lastname: Suzuki
authors.affiliation: Department of Cardiovascular Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
authors.forename: Toshiya
authors.initials: T
authors.lastname: Nishi
authors.affiliation: Department of Cardiovascular Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Nagino
authors.affiliation: Department of Cardiovascular Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
authors.forename: Kana
authors.initials: K
authors.lastname: Sasaki
authors.affiliation: Department of Cardiovascular Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Aizawa
authors.affiliation: Department of Cardiovascular Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
authors.forename: Nanae
authors.initials: N
authors.lastname: Kada
authors.affiliation: Department of Cardiovascular Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
authors.forename: Daigo
authors.initials: D
authors.lastname: Sawaki
authors.affiliation: Department of Cardiovascular Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Munemasa
authors.affiliation: Department of Cardiovascular Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Matsumura
authors.affiliation: Department of Cardiovascular Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan; Laboratory of Developmental Biology, Institute of Molecular and Cellular Biosciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Muto
authors.affiliation: Department of Cardiovascular Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
authors.forename: Masataka
authors.initials: M
authors.lastname: Sata
authors.affiliation: Department of Radiation Biology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Miyagawa
authors.affiliation: Laboratory of Developmental Biology, Institute of Molecular and Cellular Biosciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
authors.forename: Masami
authors.initials: M
authors.lastname: Horikoshi
authors.affiliation: Department of Cardiovascular Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. Electronic address: nagai-tky@umin.ac.jp.
authors.forename: Ryozo
authors.initials: R
authors.lastname: Nagai
mesh_terms: D016475:3T3 Cells; D000107:Acetylation; D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D002319:Cardiovascular System / Q000201:enzymology* / Q000378:metabolism / Q000503:physiopathology; D002460:Cell Line; D006367:HeLa Cells; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism / Q000502:physiology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D017354:Point Mutation; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism / Q000502:physiology*
chemical_list: C492214:KLF5 protein, human; D051741:Kruppel-Like Transcription Factors; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases