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Regulation of Pokemon 1 activity by sumoylation

Authors
 Hee-Eun Roh  ;  Min-Nyung Lee  ;  Man-Wook Hur  ;  Mi-Young Yu  ;  Yoo-Jin Kim  ;  Won-Il Choi  ;  Bu-Nam Jeon 
Citation
 CELLULAR PHYSIOLOGY AND BIOCHEMISTRY, Vol.20(1-4) : 167-180, 2007 
Journal Title
 CELLULAR PHYSIOLOGY AND BIOCHEMISTRY 
ISSN
 1015-8987 
Issue Date
2007
Abstract
Pokemon 1 is a proto-oncogenic transcriptional regulator that contains a POZ domain at the N-terminus and four Kruppel-like zinc fingers at the C-terminus. Pokemon 1 plays an important role in adipogenesis, osteogenesis, oncogenesis, and transcription of NF-kB responsive genes. Recent reports have shown that biological activities of transcription factors are regulated by sumolylation.We investigated whether Pokemon 1 is post-translationally modified by sumoylation and whether the modification affects Pokemon 1''s transcriptional properties. We found that Pokemon 1 is sumoylated in vitro and in vivo. Upon careful analysis of the amino acid sequence of Pokemon 1, we found ten potential sumoylation sites located at lysines 61, 354, 371, 379, 383, 396, 486, 487, 536 and 539. We mutated each of these amino acids into arginine and tested whether the mutation could affect the transcriptional properties of Pokemon 1 on the Pokemon 1 responsive genes, such as ADH5/FDH and pG5-FRE-Luc. Wild-type Pokemon 1 potently represses transcription of ADH5/FDH. Most of the mutants, however, were weaker transcription repressors and repressed transcription 1.3-3.3 fold less effective. Although potential sumoylation sites were located close to the DNA binding domain or the nuclear localization sequence, the mutations did not alter nuclear localization or DNA binding activity. In addition, on the pG5-FRE-Luc test promoter construct, ectopic SUMO-1 repressed transcription in the presence of Pokemon 1. The sumoylation target lysine residue at amino acid 61, which is located in the middle of the POZ-domain, is important because K61R mutation resulted in a much weaker molecular interaction with corepressors. Our data suggest that Pokemon 1''s activity as a transcription factor may involve sumoylation, and that sumoylation might be important in the regulation of transcription by Pokemon 1.
Full Text
http://www.karger.com/Article/Abstract/104164
DOI
10.1159/000104164
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers
Yonsei Authors
Kim, Yoo Jin(김유진)
Roh, Hee Eun(노희은)
Yu, Mi Young(유미영)
Jeon, Bu Nam(전부남)
Choi, Won Il(최원일)
Hur, Man Wook(허만욱) ORCID logo https://orcid.org/0000-0002-3416-1334
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/95820
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