Dual specificity phosphatase 1/CL100 is a direct transcriptional target of E2F-1 in the apoptotic response to oxidative stress.
E2F-1 mediates apoptosis through transcriptional regulation of its targets. We report here that E2F-1 acts as a direct transcriptional regulator of dual specificity phosphatase 1 (DUSP1; CL100), a threonine and tyrosine phosphatase that inhibits mitogen-activated protein (MAP) kinases. We found that DUSP1 is transcriptionally induced by ectopic E2F-1 expression and that extracellular signal-regulated kinase 1/2 are dephosphorylated in the presence of E2F-1 and DUSP1. E2F-1 mediates apoptosis in the cellular response to oxidative stress. DUSP1 levels are significantly increased in an E2F-1-dependent manner following oxidative stress but not other stresses examined. DUSP1 mediates the cellular response to oxidative stress. We found that E2F-1 binds to chromatin encompassing the DUSP1 promoter and greatly stimulates the promoter activity of the DUSP1 gene. In particular, E2F-1 physically binds to an E2F-1 consensus sequence and a palindromic motif in the DUSP1 promoter. Interestingly, E2F-1 is acetylated following oxidative stress. Our findings show that E2F-1 is a transcriptional activator of DUSP1 and that DUSP1 is a link between E2F-1 and MAP kinases.
Wang
Jianli
J
Department of Radiation Oncology, Center for Radiological Research, College of Physicians and Surgeons, Columbia University Medical Center, 630 West 168th Street, New York, NY 10032, USA.
Yin
David P
DP
Liu
Yu-Xin
YX
Baer
Richard
R
Yin
Yuxin
Y
D020816:Amino Acid Motifs; D017209:Apoptosis; D001483:Base Sequence; D018797:Cell Cycle Proteins / Q000502:physiology*; D045744:Cell Line, Tumor; D054638:Dual Specificity Phosphatase 1; D050687:E2F1 Transcription Factor / Q000096:biosynthesis* / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017874:Immediate-Early Proteins / Q000502:physiology*; D020935:MAP Kinase Signaling System; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism; D018384:Oxidative Stress; D010749:Phosphoprotein Phosphatases / Q000502:physiology*; D011401:Promoter Regions, Genetic; D054645:Protein Phosphatase 1; D017027:Protein Tyrosine Phosphatases / Q000502:physiology*; D014158:Transcription, Genetic; D014162:Transfection
D018797:Cell Cycle Proteins; D050687:E2F1 Transcription Factor; D017874:Immediate-Early Proteins; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; C517019:DUSP1 protein, human; D054638:Dual Specificity Phosphatase 1; D017027:Protein Tyrosine Phosphatases