Kota, Venkatesh and Sommer, Gunhild and Hazard, E. Starr and Hardiman, Gary and Twiss, Jeffery L. and Heise, Tilman (2018) SUMO Modification of the RNA-Binding Protein La Regulates Cell Proliferation and STAT3 Protein Stability. MOLECULAR AND CELLULAR BIOLOGY, 38 (2): UNSP e0012. ISSN 0270-7306, 1098-5549
Full text not available from this repository. (Request a copy)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-La-WT) 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | IRES-MEDIATED TRANSLATION; SYNDROME ANTIGEN-B; C VIRUS-RNA; MESSENGER-RNA; AUTOANTIGEN LA; MESENCHYMAL TRANSITION; AKT PHOSPHORYLATION; LAMININ B1; SERINE 366; STEM-LOOP; La autoantigen; La protein; STAT3; proliferation; ubiquitination; SSB/La; SUMO; LARP3; RNA binding; LARP; RNA-binding proteins; ubiquitin; sumoylation |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Abteilung für Pädiatrische Hämatologie, Onkologie und Stammzelltransplantation |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 23 Mar 2020 05:45 |
| Last Modified: | 23 Mar 2020 05:45 |
| URI: | https://pred.uni-regensburg.de/id/eprint/15461 |
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