Redox-mediated modification of PLZF by SUMO-1 and ubiquitin.
Earlier, we reported that the transcriptional repressor promyelocytic leukemia zinc-finger protein (PLZF) is sumoylated at position K242, and the sumoylation regulated its biological function. Here, we show that the sumoylation site can be modified by ubiquitin. The stability and nuclear localization of PLZF were regulated by the antagonistic relationship between sumoylation and ubiquitination. We observed the antagonistic effects of ubiquitin and SUMO-1 on PLZF under oxidative stress induced by serum deprivation. Thus, the choice between modification of PLZF by SUMO or ubiquitin was determined by the intracellular level of ROS, which was generated by serum deprivation that inactivated the SUMO-conjugating enzymes Uba2 and Ubc9, and resulted in decrease of sumoylation. The ubiquitination was increased under these conditions. The expression of BID, a known transcriptional target protein of PLZF, was decreased, and the consequent apoptosis was induced by the ROS generated during serum starvation. On the basis of these results, we propose that PLZF post-translational modification is controlled by intracellular ROS, and the biological function of PLZF is regulated by sumoylation and ubiquitination.
Kang
Soo Im
SI
Laboratory of Cellular and Molecular Biochemistry, School of Life Sciences and Biotechnology, Korea University, 1-5 Anam-dong, Sungbuk-ku, Seoul, 136-701, South Korea.
Choi
Hae Woong
HW
Kim
Ick Young
IY
D051023:BH3 Interacting Domain Death Agonist Protein / Q000235:genetics; D002460:Cell Line; D002467:Cell Nucleus / Q000737:chemistry / Q000378:metabolism; D015536:Down-Regulation; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D010084:Oxidation-Reduction; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D011499:Protein Processing, Post-Translational; D017382:Reactive Oxygen Species / Q000378:metabolism; D012097:Repressor Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D025842:SUMO-1 Protein / Q000378:metabolism*; D014158:Transcription, Genetic; D044764:Ubiquitin-Activating Enzymes / Q000378:metabolism; D044763:Ubiquitin-Conjugating Enzymes / Q000378:metabolism; D016335:Zinc Fingers; D000098843:Ubiquitin-Conjugating Enzyme UBC9
D051023:BH3 Interacting Domain Death Agonist Protein; C494814:BID protein, human; D051741:Kruppel-Like Transcription Factors; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D017382:Reactive Oxygen Species; D012097:Repressor Proteins; D025842:SUMO-1 Protein; C470301:UBA2 protein, human; C092037:ZBTB16 protein, human; D044763:Ubiquitin-Conjugating Enzymes; D044764:Ubiquitin-Activating Enzymes; D000098843:Ubiquitin-Conjugating Enzyme UBC9