Eukaryotic translation initiator protein 1A isoform, CCS-3, enhances the transcriptional repression of p21CIP1 by proto-oncogene FBI-1 (Pokemon/ZBTB7A).

Abstract

FBI-1, a member of the POK (POZ and Kruppel) family of transcription factors, plays a role in differentiation, oncogenesis, and adipogenesis. eEF1A is a eukaryotic translation elongation factor involved in several cellular processes including embryogenesis, oncogenic transformation, cell proliferation, and cytoskeletal organization. CCS-3, a potential cervical cancer suppressor, is an isoform of eEF1A. We found that eEF1A forms a complex with FBI-1 by co-immunoprecipitation, SDS-PAGE, and MALDI-TOF Mass analysis of the immunoprecipitate. GST fusion protein pull-downs showed that FBI-1 directly interacts with eEF1A and CCS-3 via the zinc finger and POZ-domain of FBI-1. FBI-1 co-localizes with either eEF1A or CCS-3 at the nuclear periplasm. CCS-3 enhances transcriptional repression of the p21CIP1 gene (hereafter referred to as p21) by FBI-1. The POZ-domain of FBI-1 interacts with the co-repressors, SMRT and BCoR. We found that CCS-3 also interacts with the co-repressors independently. The molecular interaction between the co-repressors and CCS-3 at the POZ-domain of FBI-1 appears to enhance FBI-1 mediated transcriptional repression. Our data suggest that CCS-3 may be important in cell differentiation, tumorigenesis, and oncogenesis by interacting with the proto-oncogene FBI-1 and transcriptional co-repressors.

• Authors: Won-Il Choi, Youngsoo Kim, Yuri Kim, Mi-young Yu, Jungeun Park, Choong-Eun Lee, Bu-Nam Jeon, Dong-In Koh, Man-Wook Hur
• Journal: Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology (Cell Physiol Biochem) Vol. 23 Issue 4-6 Pg. 359-70 ( 2009) ISSN: 1421-9778 [Electronic] Germany
• PMID: 19471103 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2009 S. Karger AG, Basel.

Chemical References

• CDKN1A protein, human
• Cyclin-Dependent Kinase Inhibitor p21
• DNA-Binding Proteins
• EEF1A1 protein, human
• MAS1 protein, human
• Peptide Elongation Factor 1
• Protein Isoforms
• Proto-Oncogene Mas
• Transcription Factors
• ZBTB7A protein, human

Topics

• Amino Acid Sequence
• Cell Differentiation
• Cyclin-Dependent Kinase Inhibitor p21 (genetics, metabolism)
• DNA-Binding Proteins (genetics, metabolism)
• Humans
• Immunoprecipitation
• Molecular Sequence Data
• Peptide Elongation Factor 1 (genetics, metabolism)
• Protein Isoforms (genetics, metabolism)
• Protein Structure, Tertiary
• Proto-Oncogene Mas
• Transcription Factors (genetics, metabolism)
• Transcription, Genetic