A new family of cyclophilins with an RNA recognition motif that interact with members of the trx/MLL protein family in Drosophila and human cells

Abstract

A new family of cyclophilins with an RNA recognition motif (RRM) has members in vertebrates, roundworms and flatworms. We have identified a Drosophilacyclophilin, Dcyp33, with a high degree of amino acid sequence identity and similarity with other members of the family. Dcyp33 interacts through its RRM domain with the third PHD finger of trithorax. This interaction is conserved in the human homologues of these proteins, Cyp33 and MLL. Over expression of Dcyp33 in DrosophilaSL1 cells results in down-regulation of AbdominalB Hoxgene expression, mirroring the effect of human Cyp33 on the expression of human HOXgenes.

A 1-Megadalton ESC/E(Z) Complex from Drosophila That Contains Polycomblike and RPD3

“…PCL contains two PHD fingers, a motif found in a wide variety of proteins (1), including the chromatin-associated trxG proteins TRX (43), ASH1 (48), and ASH2 (3) and the histone acetyltransferase CBP, where it is required for histone acetyltransferase activity (25). PHD fingers in TRX and its human homolog MLL mediate homodimerization and binding to the cyclophilin Cyp33 (4,21). A PHD finger in the KAP-1 corepressor is required for binding of KAP-1 to the Mi-2␣ subunit of the NuRD complex (38).…”

When epigenetics kills: MLL fusion proteins in leukemia

“…It is tempting to speculate that a physical separation of MLL C from MLL N could uncover the intrinsic repressor properties and therefore serve as an 'off' switch. In this regard it is interesting that the prolyl-isomerase cyclophilin33 (CYP33) was found to interact with a zinc finger structure in MLL N that is also conserved in Drosophila TRX [38,39]. These PHD (Plant homeodomain) fingers are adjacent to the MT (CxxC) region.…”

Histone recognition and nuclear receptor co-activator functions ofDrosophilaCara Mitad, a homolog of the N-terminal portion of mammalian MLL2 and MLL3

“…S3). Unlike vertebrate MLL1 and Drosophila TRX, the CMI PHDf3.b was unable to bind the cyclophilin CYP33, which is implicated in controlling MLL and TRX functions (Anderson et al, 2002;Fair et al, 2001;Hom et al, 2010;Park et al, 2010;Wang et al, 2010). Modified and unmodified histone H3 N-terminal peptides (aa 1-21) fused to biotin were used in pulldown assays to determine whether the PHDf3.b of CMI could recognize and bind H3K4me3 in vitro (Fig.…”