KRAB-Zinc Finger Proteins: A Repressor Family Displaying Multiple Biological Functions

Abstract

Zinc finger proteins containing the Kruppel associated box (KRAB-ZFPs) constitute the largest individual family of transcriptional repressors encoded by the genomes of higher organisms. KRAB domain, positioned at the NH2 terminus of the KRAB-ZFPs, interacts with a scaffold protein, KAP-1, which is able to recruit various transcriptional factors causing repression of genes to which KRAB ZFPs bind. The relevance of such repression is reflected in the large number of the KRAB zinc finger protein genes in the human genome. However, in spite of their numerical abundance little is currently known about the gene targets and the physiological functions of KRAB- ZFPs. However, emerging evidence links the transcriptional repression mediated by the KRAB-ZFPs to cell proliferation, differentiation, apoptosis and cancer. Moreover, the fact that KRAB containing proteins are vertebrate-specific suggests that they have evolved recently, and that their key roles lie in some aspects of vertebrate development. In this review, we will briefly discuss some regulatory functions of the KRAB-ZFPs in different physiological and pathological states, thus contributing to better understand their biological roles.

Keywords: Apoptosis; Evolution; KAP-1 corepressor; KRAB domain; Metabolism; Transcriptional repression; Zinc finger..

Fig. (1A)

Zinc finger-mediated binding of a typical KRAB-ZFP to the promoter target gene. (B) Recruitment to chromatin of co-regulators and ATP-dependent activities that modify chromatin (PRMTs,HDACs, SETDB1, NuRD) mediated by KRAB/KAP-1 complex.