Pellino-1, an Adaptor Protein of Interleukin-1 Receptor/toll-like Receptor Signaling, is Sumoylated by Ubc9

Overview

Journal Mol Cells

Publisher Elsevier

Specialties Cell Biology
Molecular Biology

Date 2010 Dec 2

PMID 21120624

Citations 8

Authors

Jun Hwan Kim

Ki Sa Sung

Su Myung Jung

Youn Sook Lee

Jae Young Kwon

Cheol Yong Choi

Seok Hee Park

Affiliations

Soon will be listed here.

Abstract

Covalent modifications of the Pellino-1 protein are essential for transmitting innate immune response signals downstream, as the phosphorylation and polyubiquitination of Pellino-1 mediated by the IRAK proteins appear to have roles in regulating Pellino-1 function. In this study, we demonstrate that the Pellino-1 protein is post-translationally modified by small-ubiquitin-related modifier-1 (SUMO-1). Sumoylation assays with Pellino-1 and SUMO-1 expression plasmids reveal that the Pellino-1 protein is sumoylated in vitro and in vivo. Treatment of SUMO-1 specific protease 1 (SENP1) inhibited the sumoylation of the Pellino-1 protein and a GST pull-down assay as well as a yeast two hybrid assay showed that Pellino-1 binds to the SUMO-conjugating enzyme, Ubc9. Furthermore, we identified the five lysine residues of the Pellino-1 protein where SUMO-1 covalently attaches. Some of the sumoylated sites overlap with previously identified ubiquitination sites, suggesting competition between sumoylation and ubiquitination, as well as suggesting that the sumoylated Pellino-1 protein may have a cellular function distinct from previously identified functions.

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References

Choi K, Lee Y, Lim S, Choi H, Lee C, Lee E . Smad6 negatively regulates interleukin 1-receptor-Toll-like receptor signaling through direct interaction with the adaptor Pellino-1. Nat Immunol. 2006; 7(10):1057-65. DOI: 10.1038/ni1383. View

Zhao J . Sumoylation regulates diverse biological processes. Cell Mol Life Sci. 2007; 64(23):3017-33. PMC: 7079795. DOI: 10.1007/s00018-007-7137-4. View

Kawai T, Akira S . Signaling to NF-kappaB by Toll-like receptors. Trends Mol Med. 2007; 13(11):460-9. DOI: 10.1016/j.molmed.2007.09.002. View

Rodriguez M, Dargemont C, Hay R . SUMO-1 conjugation in vivo requires both a consensus modification motif and nuclear targeting. J Biol Chem. 2001; 276(16):12654-9. DOI: 10.1074/jbc.M009476200. View

Yu K, Kwon H, Norman D, Vig E, Goebl M, Harrington M . Cutting edge: mouse pellino-2 modulates IL-1 and lipopolysaccharide signaling. J Immunol. 2002; 169(8):4075-8. DOI: 10.4049/jimmunol.169.8.4075. View

ONeill L, Bowie A . The family of five: TIR-domain-containing adaptors in Toll-like receptor signalling. Nat Rev Immunol. 2007; 7(5):353-64. DOI: 10.1038/nri2079. View

Bailey D, OHare P . Characterization of the localization and proteolytic activity of the SUMO-specific protease, SENP1. J Biol Chem. 2003; 279(1):692-703. DOI: 10.1074/jbc.M306195200. View

Hay R . SUMO: a history of modification. Mol Cell. 2005; 18(1):1-12. DOI: 10.1016/j.molcel.2005.03.012. View

Ordureau A, Smith H, Windheim M, Peggie M, Carrick E, Morrice N . The IRAK-catalysed activation of the E3 ligase function of Pellino isoforms induces the Lys63-linked polyubiquitination of IRAK1. Biochem J. 2007; 409(1):43-52. PMC: 5791886. DOI: 10.1042/BJ20071365. View

10.

Ahn J, Lee Y, Ahn J, Choi C . Covalent conjugation of Groucho with SUMO-1 modulates its corepressor activity. Biochem Biophys Res Commun. 2008; 379(1):160-5. DOI: 10.1016/j.bbrc.2008.12.043. View

11.

Melchior F . SUMO--nonclassical ubiquitin. Annu Rev Cell Dev Biol. 2000; 16:591-626. DOI: 10.1146/annurev.cellbio.16.1.591. View

12.

Bailey D, OHare P . Herpes simplex virus 1 ICP0 co-localizes with a SUMO-specific protease. J Gen Virol. 2002; 83(Pt 12):2951-2964. DOI: 10.1099/0022-1317-83-12-2951. View

13.

ONeill L, Dinarello C . The IL-1 receptor/toll-like receptor superfamily: crucial receptors for inflammation and host defense. Immunol Today. 2000; 21(5):206-9. DOI: 10.1016/s0167-5699(00)01611-x. View

14.

Johnson E . Protein modification by SUMO. Annu Rev Biochem. 2004; 73:355-82. DOI: 10.1146/annurev.biochem.73.011303.074118. View

15.

Butler M, Hanly J, Moynagh P . Kinase-active interleukin-1 receptor-associated kinases promote polyubiquitination and degradation of the Pellino family: direct evidence for PELLINO proteins being ubiquitin-protein isopeptide ligases. J Biol Chem. 2007; 282(41):29729-37. DOI: 10.1074/jbc.M704558200. View

16.

Moynagh P . The Pellino family: IRAK E3 ligases with emerging roles in innate immune signalling. Trends Immunol. 2008; 30(1):33-42. DOI: 10.1016/j.it.2008.10.001. View

17.

ONeill L . The interleukin-1 receptor/Toll-like receptor superfamily: 10 years of progress. Immunol Rev. 2009; 226:10-8. DOI: 10.1111/j.1600-065X.2008.00701.x. View

18.

Cao Z, Henzel W, Gao X . IRAK: a kinase associated with the interleukin-1 receptor. Science. 1996; 271(5252):1128-31. DOI: 10.1126/science.271.5252.1128. View

19.

Yeh E . SUMOylation and De-SUMOylation: wrestling with life's processes. J Biol Chem. 2008; 284(13):8223-7. PMC: 2659178. DOI: 10.1074/jbc.R800050200. View

20.

Jiang Z, Johnson H, Nie H, Qin J, Bird T, Li X . Pellino 1 is required for interleukin-1 (IL-1)-mediated signaling through its interaction with the IL-1 receptor-associated kinase 4 (IRAK4)-IRAK-tumor necrosis factor receptor-associated factor 6 (TRAF6) complex. J Biol Chem. 2002; 278(13):10952-6. DOI: 10.1074/jbc.M212112200. View