Regulation of hnRNPK sumoylation and activity

PELISCH FEDERICO; POZZI BERTA; SREBROW ANABELLA

MUNICH

Workshop; Computational Mass Spectrometry Based Proteomics Quantitative proteomics applied to life science and system biology; 2011

Max Planck Institute of Biochemistry

Heterogeneous nuclear ribonucleoprotein (hnRNP) K is a nucleocytoplasmic shuttling poly(rC)-binding protein that regulates gene transcription and mRNA metabolism. In fact, besides enhancing the transcription of genes (e.g.,MYC) containing a cis regulatory CT-rich promoter element, hnRNP K also regulates translation (both cap-and IRES- dependent), splicing and mRNA stability. Some of these have been reported to be regulated by cell signaling: ERK-dependent hnRNP K phosphorylation negatively regulates translation of mRNAs (e.g.,15-LOX) containing the CT-rich differentiation control element in the 3´UTR. By contrast, hnRNP K positively regulates translation of mRNAs (ie, MYC) containing an IRES with an hnRNPK-binding site. HnRNP K protein stability is regulated by the E3 ubiquitin ligase MDM2 and, by serving as a cofactor for p53, plays key roles in coordinating transcriptional responses to DNA damage. HnRNP K undergoes several post-translational modifications (PTMs): methylation, phosphorylation, ubiquitylation, and sumoylation. The main goal of my current research project is to study hnRNP K sumoylation and its consequences. We have shown that hnRNP K not only occurs in vivo but is recapitulated in an in vitro reconstituted system. Furthermore, we have mapped the sumoylation site on hnRNP K and identified the polycomb protein Pc2 as the E3 ligase activity involved in its regulation. By comparing the wild type and sumoylation-deficient hnRNPK, we plan to address the biological relevance of this modification.