3 years ago

SUMO-modification of RNA-binding protein La regulates cell proliferation and STAT3 protein stability.

Tilman Heise, Gunhild Sommer, Jeffery L Twiss, Gary Hardiman, E Starr Hazard, Venkatesh Kota
The cancer associated RNA-binding protein La is posttranslationally modified by phosphorylation and sumoylation. Sumoylation of La not only regulates the trafficking of La in neuronal axons but also its association with specific mRNAs. Depletion of La in various types of cancer cell lines impairs cell proliferation, however, the molecular mechanism whereby La supports cell proliferation is not clearly understood.In this study, we address the question whether sumoylation of La contributes to cell proliferation of HEK293 cells. We show that HEK293 cells stably expressing wild type La (gfpLa(WT)) grow faster than cells expressing a sumoylation-deficient mutant La (gfpLa(SD)) suggesting a pro-proliferative function of La in HEK293 cells.Further, we found that STAT3 protein levels were reduced in gfpLa(SD) cells due to an increase in STAT3 ubiquitination and that overexpression of STAT3 partially restored cell proliferation. Finally, we present RNA sequencing data of RNA immunoprecipitations (RIPs) and describe that mRNAs associated with cell cycle and ubiquitination are preferentially bound by gfpLa(WT) and are less enriched in gfpLa(SD) RIPs. Taken together, our study supports a novel mechanism whereby sumoylation of La promotes cell proliferation by averting ubiquitination-mediated degradation of the STAT3 protein.

Publisher URL: http://doi.org/10.1128/MCB.00129-17

DOI: 10.1128/MCB.00129-17

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