Kim S S, Chen Y M, O'Leary E, Witzgall R, Vidal M, Bonventre J V
Renal Unit, Massachusetts General Hospital, Charlestown 02129, USA.
Proc Natl Acad Sci U S A. 1996 Dec 24;93(26):15299-304. doi: 10.1073/pnas.93.26.15299.
The Krüppel-associated box A (KRAB-A) domain is an evolutionarily conserved transcriptional repressor domain present in approximately one-third of zinc finger proteins of the Cys2-His2 type. Using the yeast two-hybrid system, we report the isolation of a cDNA encoding a novel murine protein, KRAB-A interacting protein 1 (KRIP-1) that physically interacts with the KRAB-A region. KRIP-1 is a member of the RBCC subfamily of the RING finger, or Cys3HisCys4, family of zinc binding proteins whose other members are known to play important roles in differentiation, oncogenesis, and signal transduction. The KRIP-1 protein has high homology to TIF1, a putative modulator of ligand-dependent activation function of nuclear receptors. A 3.5-kb mRNA for KRIP-1 is ubiquitously expressed among all adult mouse tissues studied. When a GAL4-KRIP-1 fusion protein is expressed in COS cells with a chloramphenicol acetyltransferase reporter construct with five GAL4 binding sites, there is dose-dependent repression of transcription. Thus, KRIP-1 interacts with the KRAB-A region of C2H2 zinc finger proteins and may mediate or modulate KRAB-A transcriptional repressor activity.
克勒ppel相关盒A（KRAB - A）结构域是一种在进化上保守的转录抑制结构域，存在于约三分之一的Cys2 - His2型锌指蛋白中。利用酵母双杂交系统，我们报告分离出一个编码新型小鼠蛋白——KRAB - A相互作用蛋白1（KRIP - 1）的cDNA，该蛋白与KRAB - A区域发生物理相互作用。KRIP - 1是锌结合蛋白的RING指家族（即Cys3HisCys4家族）的RBCC亚家族成员，已知该家族的其他成员在分化、肿瘤发生和信号转导中发挥重要作用。KRIP - 1蛋白与TIF1高度同源，TIF1是核受体配体依赖性激活功能的一种假定调节因子。在所有研究的成年小鼠组织中均普遍表达一种3.5 kb的KRIP - 1 mRNA。当用带有五个GAL4结合位点的氯霉素乙酰转移酶报告构建体在COS细胞中表达GAL4 - KRIP - 1融合蛋白时，存在剂量依赖性的转录抑制。因此，KRIP - 1与C2H2锌指蛋白的KRAB - A区域相互作用，并可能介导或调节KRAB - A转录抑制活性。
