sZIP, an alternative splice variant of ZIP, antagonizes transcription repression and growth inhibition by ZIP

Wenhua Yu; Ruifang Li; Bin Gui; Yongfeng Shang

doi:10.1074/jbc.M110.107508

sZIP, an alternative splice variant of ZIP, antagonizes transcription repression and growth inhibition by ZIP

J Biol Chem. 2010 May 7;285(19):14301-7. doi: 10.1074/jbc.M110.107508. Epub 2010 Mar 16.

Authors

Wenhua Yu¹, Ruifang Li, Bin Gui, Yongfeng Shang

Affiliation

¹ Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Beijing 100191, China.

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alternative Splicing*
Blotting, Western
Carcinoma, Hepatocellular / genetics
Carcinoma, Hepatocellular / metabolism
Carcinoma, Hepatocellular / pathology*
Cation Transport Proteins / genetics*
Cation Transport Proteins / metabolism
Chromatin Immunoprecipitation
Cloning, Molecular
Colony-Forming Units Assay
DNA / genetics
DNA / metabolism
ErbB Receptors / genetics
ErbB Receptors / metabolism
Flow Cytometry
Gene Expression Regulation
HeLa Cells
Humans
Immunoprecipitation
Liver Neoplasms / genetics
Liver Neoplasms / metabolism
Liver Neoplasms / pathology*
Mi-2 Nucleosome Remodeling and Deacetylase Complex / metabolism*
RNA, Messenger / genetics
RNA, Messenger / metabolism
Repressor Proteins / genetics*
Repressor Proteins / metabolism
Reverse Transcriptase Polymerase Chain Reaction
Transcription, Genetic
Tumor Cells, Cultured

Substances

Cation Transport Proteins
RNA, Messenger
Repressor Proteins
SLC39A1 protein, human
ZGPAT protein, human
DNA
ErbB Receptors
Mi-2 Nucleosome Remodeling and Deacetylase Complex