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

Venkatesh Kota, Gunhild Sommer, E. Starr Hazard, Gary Hardiman, Jeffery L. Twiss, Tilman Heise*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)
33 Downloads (Pure)

Abstract

The cancer-associated RNA-binding protein La is posttranslationally modified by phosphorylation and sumoylation. Sumoylation of La regulates not only 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 of whether sumoylation of La contributes to cell proliferation of HEK293 cells. We show that HEK293 cells stably expressing green fluorescent protein (GFP)-tagged wild-type La (GFP-LaWT) grow faster than cells expressing a sumoylation-deficient mutant La (GFP-LaSD), suggesting a proproliferative function of La in HEK293 cells. Further, we found that STAT3 protein levels were reduced in GFP-LaSD cells due to an increase in STAT3 ubiquitination and that overexpression of STAT3 partially restored cell proliferation. Finally, we present RNA sequencing data from RNA immunoprecipitations (RIPs) and report that mRNAs associated with the cell cycle and ubiquitination are preferentially bound by GFP-LaWT and are less enriched in GFP-LaSD RIPs. Taken together, results of our study support a novel mechanism whereby sumoylation of La promotes cell proliferation by averting ubiquitination-mediated degradation of the STAT3 protein.

Original languageEnglish
Article numbere00129-17
JournalMolecular and Cellular Biology
Volume38
Issue number2
Early online date29 Dec 2017
DOIs
Publication statusPublished - 01 Jan 2018
Externally publishedYes

Keywords

  • La autoantigen
  • La protein
  • LARP
  • LARP3
  • Proliferation
  • RNA binding
  • RNA-binding proteins
  • SSB/La
  • STAT3
  • SUMO
  • Sumoylation
  • Ubiquitin
  • Ubiquitination

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Fingerprint

Dive into the research topics of 'SUMO modification of the RNA-binding protein La regulates cell proliferation and STAT3 protein stability'. Together they form a unique fingerprint.

Cite this