title: Dimerization of ZIP promotes its transcriptional repressive function and biological activity.
abstract: Self-association of a protein to form dimer and oligomer is a general theme in biological control mechanism, and is increasingly understood to be an important step in many cellular processes, including signaling transduction, protein degradation and transcriptional regulation. Previously, we cloned and functionally characterized a gene encoded for ZIP (zinc finger and G-patch domain-containing protein). We showed that ZIP is a novel transcription repressor that regulates, through recruitment of the nucleosome remodeling and deacetylase (NuRD) complex, a collection of functionally important genes including the epidermal growth factor receptor (EGFR) oncogene. The important role ZIP plays in controlling cell proliferation and carcinogenesis highlights the need for a detailed understanding of the finely mechanisms by which ZIP is regulated. Here, we report that ZIP forms homodimers in vitro and in vivo through its C-terminal domains. We demonstrated that ZIP dimerization promotes its transcriptional repressive activity and is essential for its DNA binding. We showed that enforced dimerization of ZIP suppresses EGFR expression, leading to the delay of cell cycle progression and the inhibition of breast cancer cell proliferation. Thus, our results revealed that dimerization is crucial for is transcriptional repressive function and biological activity and provided a finely tuned means for the regulation the expression of EGFR oncogene. These may shed new light on the EGFR-related breast carcinogenesis and offer a potential new target for breast cancer therapy.
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Gui
authors.forename: Xiao
authors.initials: X
authors.lastname: Han
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jing
authors.initials: J
authors.lastname: Liang
authors.forename: Dandan
authors.initials: D
authors.lastname: Wang
authors.forename: Chenghao
authors.initials: C
authors.lastname: Xuan
authors.forename: Zhipeng
authors.initials: Z
authors.lastname: Yu
authors.forename: Yongfeng
authors.initials: Y
authors.lastname: Shang
mesh_terms: D001483:Base Sequence; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000473:pathology; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D017931:DNA Primers; D019281:Dimerization; D024202:Electrophoretic Mobility Shift Assay; D005434:Flow Cytometry; D006801:Humans; D060888:Real-Time Polymerase Chain Reaction; D012097:Repressor Proteins / Q000737:chemistry / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic; D020798:Two-Hybrid System Techniques
chemical_list: D017931:DNA Primers; D012097:Repressor Proteins; C549924:ZGPAT protein, human