sZIP, an alternative splice variant of ZIP, antagonizes transcription repression and growth inhibition by ZIP.
Recently, we reported a novel transcriptional repressor, ZIP (for zinc finger and G-patch domain-containing), which recruits the Mi-2/NuRD (nucleosome remodeling and deacetylase) complex and represses the expression of epidermal growth factor receptor (EGFR). In doing so, ZIP inhibits cell proliferation and suppresses breast carcinogenesis. Here, we report the cloning and the characterization of an alternatively spliced isoform of ZIP, sZIP. sZIP is an N-terminal truncated form of ZIP, lacking the zinc finger but retaining part of the G-patch domain and C-terminal coiled-coil domain of ZIP. We showed that sZIP could interact with the NuRD complex but lost its DNA-binding capacity. We demonstrated that sZIP antagonizes the transcription repression by ZIP by competing for the binding of the NuRD complex and that sZIP alleviates the growth inhibitory effect of ZIP on hepatocarcinoma cells through attenuating the transcriptional repression of EGFR. Our data provide a finely tuned mechanism for EGFR regulation and add another player for transcription repression.
Yu
Wenhua
W
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Beijing 100191, China.
Li
Ruifang
R
Gui
Bin
B
Shang
Yongfeng
Y
D017398:Alternative Splicing; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D027682:Cation Transport Proteins / Q000235:genetics* / Q000378:metabolism; D047369:Chromatin Immunoprecipitation; D003001:Cloning, Molecular; D003114:Colony-Forming Units Assay; D004247:DNA / Q000235:genetics / Q000378:metabolism; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D047468:Immunoprecipitation; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D027682:Cation Transport Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; C403517:SLC39A1 protein, human; C549924:ZGPAT protein, human; D004247:DNA; D066246:ErbB Receptors; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex