Regulation of Egr-1 by association with the proteasome component C8.
Primary response transcription factor, Egr-1, is rapidly activated by a variety of extracellular stimuli. Activation of Egr-1 is shown to function as a master switch activated by ischemia to trigger expression of pivotal regulators of inflammation, coagulation and vascular hyperpermeability. Egr-1 is a short-lived protein, but the mechanism that regulates its stability has not yet been clarified. In this study, the yeast two-hybrid screening revealed that Egr-1 interacts significantly with PRC8 (proteasome component C8) and the specific interaction was confirmed by GST pull-down assay and coimmunoprecipitation. Interestingly, we found that the PRC8-mediated regulation of Egr-1 activity is associated with the proteasome pathway and PRC8 inhibits the transcriptional activity of Egr-1. In addition, Egr-1 protein was specifically multiubiquitinated by ubiquitin. These data strongly imply that Egr-1 protein is targeted for proteolysis by the ubiquitin-dependent proteasome pathway.
Bae
Myung-Ho
MH
Department of Molecular Biology, Pusan National University, South Korea.
Jeong
Chul-Ho
CH
Kim
Se-Hee
SH
Bae
Moon-Kyoung
MK
Jeong
Joo-Won
JW
Ahn
Mee-Young
MY
Bae
Soo-Kyung
SK
Kim
Nam Deuk
ND
Kim
Chul Woo
CW
Kim
Kwang-Rok
KR
Kim
Kyu-Won
KW
D000818:Animals; D002460:Cell Line; D003546:Cysteine Endopeptidases / Q000737:chemistry / Q000378:metabolism*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051766:Early Growth Response Protein 1; D015723:Gene Library; D006801:Humans; D017874:Immediate-Early Proteins; D007976:Leupeptins / Q000494:pharmacology; D051379:Mice; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D010447:Peptide Hydrolases / Q000737:chemistry / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection; D020798:Two-Hybrid System Techniques; D025801:Ubiquitin / Q000378:metabolism
D015853:Cysteine Proteinase Inhibitors; D004268:DNA-Binding Proteins; C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; C486109:Egr1 protein, mouse; D017874:Immediate-Early Proteins; D007976:Leupeptins; D009097:Multienzyme Complexes; D014157:Transcription Factors; D025801:Ubiquitin; D010447:Peptide Hydrolases; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde