Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università di Napoli "Federico II", Via S. Pansini 5, 80131 Napoli, Italy; ; Dipartimento di Scienze per la Biologia, la Geologia e l'Ambiente, Facoltà di Scienze, Università del Sannio, Via Port'Arsa 11, 82100 Benevento, Italy.
Curr Genomics. 2013 Jun;14(4):268-78. doi: 10.2174/13892029113149990002.
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.
锌指蛋白包含 KRAB 相关盒(KRAB-ZFPs),是高等生物基因组中最大的转录抑制因子家族之一。KRAB 结构域位于 KRAB-ZFPs 的 NH2 末端,与一种支架蛋白 KAP-1 相互作用,KAP-1 能够募集各种转录因子,导致 KRAB ZFPs 结合的基因受到抑制。这种抑制的相关性反映在人类基因组中大量的 KRAB 锌指蛋白基因上。然而,尽管它们数量众多,但目前对于 KRAB-ZFPs 的基因靶标和生理功能知之甚少。然而,新出现的证据将 KRAB-ZFPs 介导的转录抑制与细胞增殖、分化、凋亡和癌症联系起来。此外,含有 KRAB 的蛋白质是脊椎动物特有的这一事实表明,它们是最近进化而来的,它们的关键作用在于脊椎动物发育的某些方面。在这篇综述中,我们将简要讨论 KRAB-ZFPs 在不同生理和病理状态下的一些调节功能,从而有助于更好地理解它们的生物学作用。