ZNF121 interacts with ZBRK1 and BRCA1 to regulate their target genes in mammary epithelial cells.

The novel zinc finger protein 121 (ZNF121) has been demonstrated to physically and functionally associate with the MYC oncoprotein to regulate cell proliferation and likely breast cancer development. To further understand how ZNF121 functions in cell proliferation and carcinogenesis, we identified and characterized the interaction of ZNF121 with zinc finger and BRCA1‐interacting protein with a KRAB domain 1 (ZBRK1), a breast and ovarian cancer susceptibility protein 1 (BRCA1)‐interacting protein, using the yeast two‐hybrid assay and other approaches. We also found that ZNF121 bound to BRCA1. Functionally, ZFN121 suppressed the expression of ANG1 and HMGA2, two common downstream targets of ZBRK1 and BRCA1. Interestingly, ZNF121 also regulated the expression of BRCA1 and ZBRK1. These findings suggest that ZNF121 is likely a member of the BRCA1/CtIP/ZBRK1 repressor complex that plays a role in breast cancer. Zinc finger protein 121 (ZNF121) has been proved to be a MYC‐interacting protein which is implicated in breast cancer. In the current study, we found that ZNF121 not only interacts with zinc finger and BRCA1‐interacting protein with a KRAB domain 1 (ZBRK1) and breast and ovarian cancer susceptibility protein 1 (BRCA1), but also represses the expression of ANG1 and HMGA2, which are targets of the ZBRK1/BRCA1/CtIP complex, suggesting that ZNF121 is likely to be another member of this complex. [ABSTRACT FROM AUTHOR]