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.

Abstract

Pontin (also known as RUVBL1 and RVB1) and Reptin (also called RUVBL2 and RVB2) are related members of the large AAA+ (adenosine triphosphatase associated with diverse cellular activities) superfamily of conserved proteins. Various cellular functions depend on Pontin and Reptin, mostly because of their functions in the assembly of protein complexes that play a role in the regulation of cellular energetic metabolism, transcription, chromatin remodeling, and the DNA damage response. Little is known, though, about the interconnections between these multiple functions, how the relevant signaling pathways are regulated, whether the interconnections are affected in human disease, and whether components of these pathways are suitable targets for therapeutic intervention. The First International Workshop on Pontin (RUVBL1) and Reptin (RUVBL2), held between 16 and 19 October 2012, discussed the nature of the oligomeric organization of these proteins, their structures, their roles as partners in various protein complexes, and their involvement in cellular regulation, signaling, and pathophysiology, as well as their potential for therapeutic targeting. A major outcome of the meeting was a general consensus that most functions of Pontin and Reptin are related to their roles as chaperones or adaptor proteins that are important for the assembly and function of large signaling protein complexes.

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

“…Electrophoretic mobility gel shift assays showed that Reptin or Pontin monomers form complexes with nucleosome-DNA substrates (Fig. 1, C and D, lanes [1][2][3][4] in the same range of protein concentrations needed for binding to naked DNA (Fig. 1, C and D, lanes [13][14][15][16].…”

A Novel Interaction of Ecdysoneless (ECD) Protein with R2TP Complex Component RUVBL1 Is Required for the Functional Role of ECD in Cell Cycle Progression

“…Recent studies have shown that, aside from the R2TP complex, RUVBL1/2 are also parts of other functionally relevant complexes, such as chromatin remodeling complexes TIP60, SWR/SRCAP, and INO80 and the Fanconi anemia core complex that controls DNA interstrand cross-link repair and function, and regulate telomerase biogenesis and mitosis (19,(43)(44)(45). Given the PIH1D1-independent interaction of ECD with RUVBL1, the potential roles of ECD via these alternative complexes will be of great future interest.…”

Structure of Yin Yang 1 Oligomers That Cooperate with RuvBL1-RuvBL2 ATPases

“…These AAAϩ ATPases are implicated in several cellular processes as part of large macromolecular assemblies, such as INO80, SWR1, TIP60, and R2TP complexes, among others (20,21). Despite both proteins being essential, not much is known about their mechanism of action, and the functional significance of the several oligomeric forms of RuvBL1 and RuvBL2 is still unclear (20,21). We tested the interaction of YY1 with the RuvBL1 and RuvBL2 ATPases, showing that this interaction takes place also with purified YY1 oligomers.…”

“…RuvB assembles as hexameric rings, and its DNA-dependent ATPase activity provides the energy for branch migration (22). RuvBL1 and RuvBL2 are essential in multiple processes including transcription, DNA repair, and nonsense-mediated mRNA decay, and their overexpression is associated with tumorigenesis (20,21).…”

“…Yet YY1 could also have a direct role in DNA damage responses as it has been shown that YY1-INO80 complexes may function in DNA repair by homologous recombination (HR) (15). INO80 is a multisubunit chromatin-remodeling complex that includes, in addition to YY1 and the Ino80 catalytic subunit, RuvBL1 and RuvBL2 (18,19), two closely related (65% sequence similarity) AAAϩ (ATPases associated with diverse cellular activities) proteins (20,21). They share homology with RuvB, the prokaryotic helicase involved in Holliday junction (HJ) resolution during HR.…”