The RNA-binding protein SERBP1 interacts selectively with the signaling protein RACK1

Abstract

The RACK1 protein interacts with numerous proteins involved in signal transduction, the cytoskeleton, and mRNA splicing and translation. We used the 2-hybrid system to identify additional proteins interacting with RACK1 and isolated the RNA-binding protein SERBP1. SERPB1 shares amino acid sequence homology with HABP4 (also known as Ki-1/57), a component of the RNA spicing machinery that has been shown previously to interact with RACK1. Several different isoforms of SERBP1, generated by alternative mRNA splicing, interacted with RACK1 with indistinguishable interaction strength, as determined by a 2-hybrid beta-galactosidase assay. Analysis of deletion constructs of SERBP1 showed that the C-terminal third of the SERBP1 protein, which contains one of its two substrate sites for protein arginine N-methyltransferase 1 (PRMT1), is necessary and sufficient for it to interact with RACK1. Analysis of single amino acid substitutions in RACK1, identified in a reverse 2-hybrid screen, showed very substantial overlap with those implicated in the interaction of RACK1 with the cAMP-selective phosphodiesterase PDE4D5. These data are consistent with SERBP1 interacting selectively with RACK1, mediated by an extensive interaction surface on both proteins.

Capturing the Asc1p/Receptor for Activated C Kinase 1 (RACK1) Microenvironment at the Head Region of the 40S Ribosome with Quantitative BioID in Yeast

“…The BioID analyses suggest that Stm1p is deposited close to Asc1p within the 40S ribosomal head region when mRNAs are actively translated and might be kept there in standby until starvation signaling moves it into its clamping position. For Hela cells, a physical interaction of RACK1 with the Stm1p-homologous part of the putative human ortholog SERBP1 was reported just recently (55).…”

The RNA-binding protein SERBP1 functions as a novel oncogenic factor in glioblastoma by bridging cancer metabolism and epigenetic regulation

“…Vig and vig2, SERBP1 Drosophila homologs, encode RNAi complex components that are involved in heterochromatin formation [17] and were recently identified in a CRISPR screening for histone gene regulators [18]. SERBP1 also was identified as a partner of Receptor for Activated C Kinase 1 (RACK1) in a two-hybrid screening [19] and interacts with arginine-methylated and stress granule-associated proteins like heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) and fragile X mental retardation protein (FMR1) [20]. SERBP1 also interacts with ribosomal proteins, congruent with its role in regulating translation [14].…”

Analysis of eEF1Bγ interactome in the nuclear fraction of A549 human lung adenocarcinoma cells

“…SERBP1 (Serpine1 mRNA Binding Protein 1) binds different protein partners which participate in different cellular processes. For instance, it interacts with signaling protein RACK1 involved to signal transduction, mRNA splicing and translation and the cytoskeleton [78]. It interacts with SPIN1, a maternal protein containing Tudor-like domains, which is involved in regulating maternal transcripts to control meiotic resumption by controlling mRNA stability and/or translation [79].…”