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https://hdl.handle.net/2440/24077
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Type: | Journal article |
Title: | ZNF652, a novel zinc finger protein, interacts with the putative breast tumor suppressor CBFA2T3 to repress transcription |
Author: | Kumar, R. Manning, J. Spendlove, H. Kremmidiotis, G. McKirdy, R. Lee, J. Millband, D. Cheney, K. Stampfer, M. Dwivedi, P. Morris, H. Callen, D. |
Citation: | Molecular Cancer Research, 2006; 4(9):655-665 |
Publisher: | Amer Assoc Cancer Research |
Issue Date: | 2006 |
ISSN: | 1541-7786 1557-3125 |
Statement of Responsibility: | Raman Kumar, Jantina Manning, Hayley E. Spendlove, Gabriel Kremmidiotis, Ross McKirdy, Jaclyn Lee, David N. Millband, Kelly M. Cheney, Martha R. Stampfer, Prem P. Dwivedi, Howard A. Morris, and David F. Callen |
Abstract: | The transcriptional repressor CBFA2T3 is a putative breast tumor suppressor. To define the role of CBFA2T3, we used a segment of this protein as bait in a yeast two-hybrid screen and identified a novel uncharacterized protein, ZNF652. In general, primary tumors and cancer cell lines showed lower expression of ZNF652 than normal tissues. Together with the location of this gene on the long arm of chromosome 17q, a region of frequent loss of heterozygosity in cancer, these results suggest a possible role of ZNF652 in tumorigenesis. In silico analysis of this protein revealed that it contains multiple classic zinc finger domains that are predicted to bind DNA. Coimmunoprecipitation assays showed that ZNF652 strongly interacts with CBFA2T3 and this interaction occurs through the COOH-terminal 109 amino acids of ZNF652. In contrast, there was a weak interaction of ZNF652 with CBFA2T1 and CBFA2T2, the other two members of this ETO family. Transcriptional reporter assays further confirmed the strength and selectivity of the ZNF652-CBFA2T3 interaction. The transcriptional repression of growth factor independent-1 (GFI-1), a previously characterized ETO effector zinc finger protein, was shown to be enhanced by CBFA2T1, but to a lesser extent by CBFA2T2 and CBFA2T3. We therefore suggest that each of the various gene effector zinc finger proteins may specifically interact with one or more of the ETO proteins to generate a defined range of transcriptional repressor complexes. |
Keywords: | Animals Rabbits Humans Mice Rats Breast Neoplasms DNA-Binding Proteins Proto-Oncogene Proteins Tumor Suppressor Proteins Phosphoproteins Transcription Factors Repressor Proteins Two-Hybrid System Techniques Transcription, Genetic Amino Acid Sequence Zinc Fingers Genes, Tumor Suppressor Molecular Sequence Data RUNX1 Translocation Partner 1 Protein |
Description: | © 2006 American Association for Cancer Research |
DOI: | 10.1158/1541-7786.MCR-05-0249 |
Published version: | http://mcr.aacrjournals.org/cgi/content/abstract/4/9/655 |
Appears in Collections: | Aurora harvest 6 Molecular and Biomedical Science publications |
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