Serum response factor is modulated by the SUMO-1 conjugation system.
Serum stimulation leads to activation of the serum response factor (SRF)-mediated transcription of immediate-early genes such as c-fos via various signal transduction pathways. We have previously reported that promyelocytic leukemia protein (PML) is involved in the transcriptional regulation by SRF. PML is one of the well-known substrates for modification by small ubiquitin-related modifier-1 (SUMO-1) and several SUMO-1-modified proteins associate with PML. Here, we report that SRF is modified by SUMO-1 chiefly at lysine(147) within the DNA-binding domain. Substitution of this target lysine for alanine did not affect the translocation of SRF to PML-nuclear bodies. The SRF mutant augmented the transcriptional activity under Rho A-stimulated condition but not under serum-starved condition, suggesting that activated SRF is suppressed by its sumoylation. These data support the transcriptional role of SUMO-1 conjugating system in cellular serum response.
Matsuzaki
Kazuhito
K
Department of Regeneration Medicine, Institute of Molecular Embryology and Genetics, Kumamoto University, 2-2-1 Honjo, 860-0811, Kumamoto, Japan.
Minami
Takeshi
T
Tojo
Masahide
M
Honda
Yoshiomi
Y
Uchimura
Yasuhiro
Y
Saitoh
Hisato
H
Yasuda
Hideyo
H
Nagahiro
Shinji
S
Saya
Hideyuki
H
Nakao
Mitsuyoshi
M
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D018076:DNA, Complementary / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D066298:In Vitro Techniques; D008239:Lysine / Q000737:chemistry; D009363:Neoplasm Proteins / Q000378:metabolism; D009687:Nuclear Proteins; D000071156:Promyelocytic Leukemia Protein; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D025842:SUMO-1 Protein / Q000235:genetics / Q000378:metabolism*; D026362:Serum Response Factor / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D025521:Tumor Suppressor Proteins
D018076:DNA, Complementary; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D000071156:Promyelocytic Leukemia Protein; D011994:Recombinant Proteins; D025842:SUMO-1 Protein; D026362:Serum Response Factor; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C070576:PML protein, human; D008239:Lysine