RVBs 对于组装一个功能性的 TIP60 复合物是必需的。
RVBs are required for assembling a functional TIP60 complex.
机构信息
Department of Biochemistry and Molecular Genetics, University of Virginia, School of Medicine, Charlottesville, Virginia, USA.
出版信息
Mol Cell Biol. 2013 Mar;33(6):1164-74. doi: 10.1128/MCB.01567-12. Epub 2013 Jan 7.
RVB1/RVB2 (RuvBL1/RuvBL2 or pontin/reptin) are enigmatic AAA(+) ATPase proteins that are present in multiple cellular complexes. Although they have been implicated in many cellular functions, the exact molecular function of RVB proteins in the various complexes is not clear. TIP60 complex (TIP60.com) is a tumor suppressor chromatin-remodeling complex containing RVB proteins. RVBs are required for the lysine acetyltransferase activity of TIP60.com but not for that of the pure recombinant TIP60 polypeptide. Here we describe two molecular functions of RVBs in TIP60.com. First, RVBs negate the repression of catalytic activity of TIP60 by another protein in TIP60.com, p400. RVBs competitively displace the SNF2 domain of p400 from the TIP60 polypeptide. In addition RVBs are also required for heat stability of TIP60.com by a p400-independent pathway. RVB1 and RVB2 are redundant with each other for these functions and do not require their ATPase activities. Thus, RVB proteins act as molecular adaptors that can substitute for one another to facilitate the optimal assembly, heat stability, and function of the TIP60 complex.
RVB1/RVB2（RuvBL1/RuvBL2 或 pontin/reptin）是神秘的 AAA(+)ATP 酶蛋白，存在于多种细胞复合物中。尽管它们已被牵连到许多细胞功能中，但 RVB 蛋白在各种复合物中的确切分子功能尚不清楚。TIP60 复合物（TIP60.com）是一种肿瘤抑制因子染色质重塑复合物，包含 RVB 蛋白。RVB 蛋白对于 TIP60.com 的赖氨酸乙酰转移酶活性是必需的，但对于纯重组 TIP60 多肽则不是必需的。在这里，我们描述了 RVB 在 TIP60.com 中的两个分子功能。首先，RVB 蛋白可以消除 TIP60.com 中另一种蛋白质 p400 对催化活性的抑制作用。RVB 蛋白竞争性地将 p400 的 SNF2 结构域从 TIP60 多肽上置换下来。此外，RVB 蛋白还通过一种不依赖于 p400 的途径，对 TIP60.com 的热稳定性也是必需的。RVB1 和 RVB2 在这些功能上彼此冗余，并不需要它们的 ATP 酶活性。因此，RVB 蛋白充当分子衔接物，可以相互替代，以促进 TIP60 复合物的最佳组装、热稳定性和功能。
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