RVBs Are Required for Assembling a Functional TIP60 Complex

Abstract

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.

Splice variants of the SWR1-type nucleosome remodeling factor Domino have distinct functions during Drosophila melanogaster oogenesis

“…These features are also present in the C-terminus of p400 (EP400), the second human SWR1 ortholog, but are absent in either DOM-B or SRCAP (Eissenberg et al, 2005). Remarkably, p400 interacts directly with TIP60 (Jha et al, 2013) and the SANT domain of p400 inhibits TIP60 catalytic activity (Park et al, 2010), providing an interesting lead for further investigation of DOM isoforms and TIP60 interactions.…”

The Emergence of the Conserved AAA+ ATPases Pontin and Reptin on the Signaling Landscape Meeting Information: The First International Workshop on Pontin (RUVBL1) and Reptin (RUVBL2) took place at the European Institute for Chemistry and Biology in Pessac, France, 16 to 19 October 2012.

“…The Pontin and Reptin subunits of NuA4 are essential for the acetyltransferase activity of the TIP60 subunit during DNA repair (8) and also contribute to the assembly and structural organization of the NuA4 complex (9). Knocking down Pontin and Reptin in cultured human cells decreased the acetyltransferase activity of the NuA4 complex, leading to increased longevity and abundance of the phosphorylated form of the histone H2AX after DNA damage.…”

Reptin and Pontin Oligomerization and Activity Are Modulated through Histone H3 N-terminal Tail Interaction

“…An overall hexameric molecule comprises monomers connected through interactions of DI to DIII domains from adjacent subunits, encircling one ADP unit. Little is known about which forms function in vivo; evidence has been obtained for the existence of hexamers and dodecamers (18,22,23) but so far not for monomers.…”

“…Similar results were observed for Pontin. 5 Biological activities of the Reptin and Pontin proteins are generally inferred from the function of factors with which they associate (23)(24)(25). Mechanisms through which Reptin and Pontin exercise their activities are far from being understood.…”

“…Mechanisms through which Reptin and Pontin exercise their activities are far from being understood. A role in the proper assembly of the multicomponent chromatin remodeling complexes, INO80 and Tip60, has been proposed (4,7,23), but no link with the enzymatic activities of the Reptin/ Pontin has yet been established.…”