Carpenter Brian, Hill Kathryn J, Charalambous Marika, Wagner Kate J, Lahiri Diya, James Dominic I, Andersen Jens S, Schumacher Valérie, Royer-Pokora Brigitte, Mann Matthias, Ward Andrew, Roberts Stefan G E
School of Biological Sciences, University of Manchester, G.186 Stopford Building, Oxford Road, Manchester M13 9PT, UK.
Mol Cell Biol. 2004 Jan;24(2):537-49. doi: 10.1128/MCB.24.2.537-549.2004.
The Wilms' tumor suppressor protein WT1 is a transcriptional regulator that plays a key role in the development of the kidneys. The transcriptional activation domain of WT1 is subject to regulation by a suppression region within the N terminus of WT1. Using a functional assay, we provide direct evidence that this requires a transcriptional cosuppressor, which we identify as brain acid soluble protein 1 (BASP1). WT1 and BASP1 associate within the nuclei of cells that naturally express both proteins. BASP1 can confer WT1 cosuppressor activity in transfection assays, and elimination of endogenous BASP1 expression augments transcriptional activation by WT1. BASP1 is present in the developing nephron structures of the embryonic kidney and, coincident with that of WT1, its expression is restricted to the highly specialized podocyte cells of the adult kidney. Taken together, our results show that BASP1 is a WT1-associated factor that can regulate WT1 transcriptional activity.
威尔姆斯瘤抑制蛋白WT1是一种转录调节因子,在肾脏发育中起关键作用。WT1的转录激活结构域受WT1 N端一个抑制区域的调控。通过功能测定,我们提供了直接证据,表明这需要一种转录共抑制因子,我们将其鉴定为脑酸溶性蛋白1(BASP1)。WT1和BASP1在天然表达这两种蛋白的细胞核内相互作用。在转染实验中,BASP1可赋予WT1共抑制活性,消除内源性BASP1表达可增强WT1的转录激活作用。BASP1存在于胚胎肾发育中的肾单位结构中,与WT1一样,其表达仅限于成年肾脏高度特化的足细胞。综上所述,我们的结果表明BASP1是一种与WT1相关的因子,可调节WT1的转录活性。