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The EMBO journal
Nov 28, 2012;31 (23): 4441-52.

SUMOylation of hnRNP-K is required for p53-mediated cell-cycle arrest in response to DNA damage.

Seong Won Lee, Moon Hee Lee, Jong Ho Park, Sung Hwan Kang, Hee Min Yoo, Seung Hyun Ka, Young Mi Oh, Young Joo Jeon, Chin Ha Chung
Author Information
  1. Seong Won Lee: Department of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul, Korea.
PMID: 23092970 DOI: 10.1038/emboj.2012.293

Abstract

Heterogeneous ribonucleoprotein-K (hnRNP-K) is normally ubiquitinated by HDM2 for proteasome-mediated degradation. Under DNA-damage conditions, hnRNP-K is transiently stabilized and serves as a transcriptional co-activator of p53 for cell-cycle arrest. However, how the stability and function of hnRNP-K is regulated remained unknown. Here, we demonstrated that UV-induced SUMOylation of hnRNP-K prevents its ubiquitination for stabilization. Using SUMOylation-defective mutant and purified SUMOylated hnRNP-K, SUMOylation was shown to reduce hnRNP-K's affinity to HDM2 with an increase in that to p53 for p21-mediated cell-cycle arrest. PIAS3 served as a small ubiquitin-related modifier (SUMO) E3 ligase for hnRNP-K in an ATR-dependent manner. During later periods after UV exposure, however, SENP2 removed SUMO from hnRNP-K for its destabilization and in turn for release from cell-cycle arrest. Consistent with the rise-and-fall of both SUMOylation and stability of hnRNP-K, its ability to interact with PIAS3 was inversely correlated to that with SENP2 during the time course after UV exposure. These findings indicate that SUMO modification plays a crucial role in the control of hnRNP-K's function as a p53 co-activator in response to DNA damage by UV.

References

  1. Mol Med. 2000 Sep;6(9):736-49 [PMID: 11071269]
  2. Nat Rev Mol Cell Biol. 2007 Dec;8(12):947-56 [PMID: 18000527]
  3. Nat Rev Cancer. 2009 Oct;9(10):749-58 [PMID: 19776744]
  4. Curr Opin Cell Biol. 2001 Dec;13(6):738-47 [PMID: 11698191]
  5. Cell Death Differ. 2011 Jun;18(6):1005-15 [PMID: 21183956]
  6. Cell Mol Life Sci. 2009 Sep;66(18):3029-41 [PMID: 19526197]
  7. Science. 1997 Dec 5;278(5344):1803-5 [PMID: 9388184]
  8. Nature. 1992 Jul 2;358(6381):15-6 [PMID: 1614522]
  9. Mol Cell Biol. 1992 Jan;12(1):164-71 [PMID: 1729596]
  10. Clin Cancer Res. 2008 Aug 1;14(15):4694-704 [PMID: 18676737]
  11. Mol Oncol. 2011 Jun;5(3):256-64 [PMID: 21497567]
  12. EMBO J. 2002 Oct 15;21(20):5487-97 [PMID: 12374749]
  13. Nat Rev Mol Cell Biol. 2010 Dec;11(12):861-71 [PMID: 21102611]
  14. FEBS Lett. 1997 Feb 17;403(2):113-5 [PMID: 9042948]
  15. Annu Rev Biochem. 2004;73:355-82 [PMID: 15189146]
  16. Nat Rev Mol Cell Biol. 2008 Aug;9(8):616-27 [PMID: 18594563]
  17. Bioessays. 2004 Jun;26(6):629-38 [PMID: 15170860]
  18. Nat Cell Biol. 2006 Nov;8(11):1284-90 [PMID: 17013376]
  19. J Biol Chem. 2012 Aug 31;287(36):30789-99 [PMID: 22825850]
  20. J Biol Chem. 1999 Dec 31;274(53):37538-43 [PMID: 10608806]
  21. J Biol Chem. 2004 Jun 4;279(23):24873-80 [PMID: 15140884]
  22. Proc Natl Acad Sci U S A. 2006 Jul 5;103(27):10151-10152 [PMID: 16801534]
  23. DNA Repair (Amst). 2004 Aug-Sep;3(8-9):883-7 [PMID: 15279773]
  24. Oncogene. 1999 Dec 13;18(53):7644-55 [PMID: 10618704]
  25. Curr Opin Cell Biol. 2001 Apr;13(2):225-31 [PMID: 11248557]
  26. Nature. 2009 Mar 26;458(7237):461-7 [PMID: 19325626]
  27. Mol Cell. 2010 Aug 13;39(3):333-45 [PMID: 20705237]
  28. Annu Rev Cell Dev Biol. 2006;22:159-80 [PMID: 16753028]
  29. Genes Dev. 2011 Mar 1;25(5):409-33 [PMID: 21363960]
  30. Nucleic Acids Res. 2010 Aug;38(14):4708-21 [PMID: 20371517]
  31. Nature. 2002 Sep 12;419(6903):135-41 [PMID: 12226657]
  32. J Cell Physiol. 2002 Jun;191(3):257-68 [PMID: 12012321]
  33. Oncogene. 2002 Mar 27;21(13):2000-8 [PMID: 11960372]
  34. EMBO J. 1997 Jun 16;16(12):3587-98 [PMID: 9218800]
  35. PLoS Biol. 2008 Dec 16;6(12):e310 [PMID: 19090619]
  36. Mol Cell. 2005 Apr 1;18(1):1-12 [PMID: 15808504]
  37. Mol Cell Biol. 2004 May;24(9):3623-32 [PMID: 15082759]
  38. Clin Res Hepatol Gastroenterol. 2011 May;35(5):393-8 [PMID: 21334998]
  39. Oncogene. 2007 Feb 26;26(9):1306-16 [PMID: 17322916]
  40. J Biol Chem. 2009 Mar 27;284(13):8223-7 [PMID: 19008217]
  41. Mol Cell. 2010 Oct 22;40(2):179-204 [PMID: 20965415]
  42. Mol Cell. 2012 Feb 10;45(3):422-32 [PMID: 22285753]
  43. Cell Cycle. 2008 May 1;7(9):1133-8 [PMID: 18418048]
  44. Oncogene. 1998 Aug 27;17(8):931-9 [PMID: 9747872]
  45. Nat Cell Biol. 2006 Dec;8(12):1424-31 [PMID: 17086174]
  46. Oncogene. 2003 Jan 23;22(3):319-29 [PMID: 12545153]
  47. Cell. 2000 Sep 15;102(6):753-63 [PMID: 11030619]
  48. Trends Biochem Sci. 2007 Jun;32(6):286-95 [PMID: 17499995]
  49. Curr Opin Struct Biol. 2007 Dec;17(6):726-35 [PMID: 17919899]
  50. Mol Cancer Res. 2004 Jan;2(1):9-19 [PMID: 14757841]
  51. Cell. 2000 Dec 8;103(6):843-52 [PMID: 11136970]
  52. Genes Dev. 2001 Dec 1;15(23):3053-8 [PMID: 11731472]
  53. Genes Dev. 2001 Sep 1;15(17):2177-96 [PMID: 11544175]
  54. Nature. 2000 Nov 16;408(6810):307-10 [PMID: 11099028]
  55. Proc Natl Acad Sci U S A. 2004 Jun 8;101(23):8551-6 [PMID: 15161980]
  56. Cell. 2005 Dec 16;123(6):1065-78 [PMID: 16360036]
  57. Cancer Cell. 2009 Mar 3;15(3):171-83 [PMID: 19249676]
  58. Nat Rev Cancer. 2002 Aug;2(8):594-604 [PMID: 12154352]
  59. Cell. 2009 May 15;137(4):609-22 [PMID: 19450511]

MeSH Term

Cell Cycle
Cyclin-Dependent Kinase Inhibitor p21
Cysteine Endopeptidases
DNA Damage
HEK293 Cells
HeLa Cells
Heterogeneous-Nuclear Ribonucleoprotein K
Humans
Models, Biological
Molecular Chaperones
Mutation
Protein Inhibitors of Activated STAT
Small Ubiquitin-Related Modifier Proteins
Sumoylation
Tumor Suppressor Protein p53
Ubiquitin
Ultraviolet Rays

Chemicals

CDKN1A protein, human
Cyclin-Dependent Kinase Inhibitor p21
Heterogeneous-Nuclear Ribonucleoprotein K
Molecular Chaperones
PIAS3 protein, human
Protein Inhibitors of Activated STAT
Small Ubiquitin-Related Modifier Proteins
TP53 protein, human
Tumor Suppressor Protein p53
Ubiquitin
Cysteine Endopeptidases
SENP2 protein, human
Journal Article Research Support, Non-U.S. Gov't
Article has an altmetric score of 1

Word Cloud

Created with Highcharts 10.0.0hnRNP-Kcell-cyclearrestSUMOylationp53SUMOUVHDM2co-activatorstabilityfunctionhnRNP-K'sPIAS3exposureSENP2responseDNAdamageHeterogeneousribonucleoprotein-Knormallyubiquitinatedproteasome-mediateddegradationDNA-damageconditionstransientlystabilizedservestranscriptionalHoweverregulatedremainedunknowndemonstratedUV-inducedpreventsubiquitinationstabilizationUsingSUMOylation-defectivemutantpurifiedSUMOylatedshownreduceaffinityincreasep21-mediatedservedsmallubiquitin-relatedmodifierE3ligaseATR-dependentmannerlaterperiodshoweverremoveddestabilizationturnreleaseConsistentrise-and-fallabilityinteractinverselycorrelatedtimecoursefindingsindicatemodificationplayscrucialrolecontrolrequiredp53-mediated

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