ZNF652, A Novel Zinc Finger Protein, Interacts with the Putative Breast Tumor Suppressor CBFA2T3 to Repress Transcription

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. (Mol Cancer Res 2006;4(9):655 -65)

Mutant p53 drives invasion in breast tumors through up-regulation of miR-155

“…This suggests that these four miR-155 • mutant p53 targets drive pathways that prevent breast cancer invasion and metastasis. ZNF652 was considered an excellent candidate for further investigation as this gene encodes a classical zinc-finger DNA binding transcription factor that functions as a transcriptional repressor (17,18), potentially orchestrating downstream pathways of the miR-155 • mutant p53 axis.…”

“…ZNF652 is a repressor of gene transcription (17), and we hypothesised that this transcription factor may suppress invasion and metastasis through constitutive repression of key drivers of mesenchymal transformation. Identification of the key ZNF6562 targets will further elucidate the downstream regulatory network responsible for metastasis in mutant p53-miR-155 expressing breast tumors.…”

Oral Cancer Biomarkers - as Powerful Diagnostic and Prognostic Tools

“…A number of recent studies suggest new zinc finger proteins with novel structural and functional properties [83], for instance studies report that ZNF652 regulate CBFA2T3 protein leading to the promotion of tumorigenesis [85]. Another zinc finger protein, ZNF278 also activates cell growth and proliferation and its knockdown leads to suppression of cell proliferation [86].…”

Co-expression of the androgen receptor and the transcription factor ZNF652 is related to prostate cancer outcome

“…We have characterised ZNF652, a C 2 H 2 classical zinc finger protein that was initially identified in a breast expression library as an interacting partner with CBFA2T3 (MTG16) (8). CBFA2T3 is a breast cancer tumor suppressor (9) and functions as a potent transcriptional repressor complex by recruitment of various co-repressors, for example SIN3A and NCOR1, and histone deacetylases (10).…”

“…An association of CBFA2T3 with cancer is supported by its role as a breast cancer tumor suppressor (9) and involvement in a specific translocation with RUNX1 in acute myeloid leukaemia (AML) (11). Since ZNF652 is a specific effector of CBFA2T3 repressor complex function, the expression of ZNF652 in a limited data set of various tissue normal/ tumor pairs was determined (8). In a subsequent immunohistochemistry-based study, there was significant variation in expression of ZNF652 in vulvar carcinoma but no significant relationship with survival was detected (12).…”