Phosphorylation of NF-κB p65 at Ser468 controls its COMMD1-dependent ubiquitination and target gene-specific proteasomal elimination

EMBO Reports

Volumn 10, Issue 4, 2009, Pages 381-386

  Geng, Hui ^a   Wittwer, Tobias ^a   Dittrich Breiholz, Oliver ^b   Kracht, Michael ^c   Schmitz, Michael Lienhard ^a  

^a JUSTUS LIEBIG UNIVERSITY   (Germany)

^b HANNOVER MEDICAL SCHOOL   (Germany)

^c JUSTUS LIEBIG UNIVERSITY GIESSEN   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

CULLIN; CULLIN 2; CYCLOHEXIMIDE; INTERCELLULAR ADHESION MOLECULE 1; PROTEIN COMM DOMAIN 1; SERINE PROTEINASE; TRANSCRIPTION FACTOR RELA; TUMOR NECROSIS FACTOR; UBIQUITIN PROTEIN LIGASE; UNCLASSIFIED DRUG; COMMD1 PROTEIN, MOUSE; INTERLEUKIN 1; LIPOPOLYSACCHARIDE; PROTEASOME; PROTEIN; RELA PROTEIN, MOUSE; TUMOR NECROSIS FACTOR ALPHA;

ANIMAL CELL; ARTICLE; BINDING AFFINITY; CHROMATIN IMMUNOPRECIPITATION; CONCENTRATION RESPONSE; CONTROLLED STUDY; MOUSE; NONHUMAN; POINT MUTATION; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; PROTEIN STABILITY; PROTEIN TARGETING; UBIQUITINATION; ANIMAL; CELL CULTURE; DNA MICROARRAY; DRUG EFFECT; GENETICS; METABOLISM; PHOSPHORYLATION; PROMOTER REGION;

ANIMALS; CELLS, CULTURED; CHROMATIN IMMUNOPRECIPITATION; INTERLEUKIN-1; LIPOPOLYSACCHARIDES; MICE; OLIGONUCLEOTIDE ARRAY SEQUENCE ANALYSIS; PHOSPHORYLATION; PROMOTER REGIONS, GENETIC; PROTEASOME ENDOPEPTIDASE COMPLEX; PROTEINS; TRANSCRIPTION FACTOR RELA; TUMOR NECROSIS FACTOR-ALPHA; UBIQUITINATION;

EID: 64049112777     PISSN: 1469221X     EISSN: 14693178     Source Type: Journal    
DOI: 10.1038/embor.2009.10     Document Type: Article

References (24)

1. Buss H, Dorrie A, Schmitz ML, Frank R, Livingstone M, Resch K, Kracht M (2004) Phosphorylation of serine 468 by GSK-3β negatively regulates basal p65 NF-κB activity. J Biol Chem 279: 49571-49574
2. Carmody RJ, Ruan Q, Palmer S, Hilliard B, Chen YH (2007) Negative regulation of toll-like receptor signaling by NF-κB p50 ubiquitination blockade. Science 317: 675-678
3. Franzoso G, Biswas P, Poli G, Carlson LM, Brown KD, Tomita-Yamaguchi M, Fauci AS, Siebenlist UK (1994) A family of serine proteases expressed exclusively in myelo-monocytic cells specifically processes the nuclear factor-κ B subunit p65 in vitro and may impair human immunodeficiency virus replication in these cells. J Exp Med 180: 1445-1456
4. Hacker H, Karin M (2006) Regulation and function of IKK and IKK-related kinases. Sci STKE 2006: 13
5. Hayden MS, Ghosh S (2008) Shared principles in NF-κB signaling. Cell 132: 344-362
6. Krappmann D, Scheidereit C (2005) A pervasive role of ubiquitin conjugation in activation and termination of IκB kinase pathways. EMBO Rep 6: 321-326
7. Lang V, Janzen J, Fischer GZ, Soneji Y, Beinke S, Salmeron A, Allen H, Hay RT, Ben-Neriah Y, Ley SC (2003) TrCP-mediated proteolysis of NF-κB1 p105 requires phosphorylation of p105 serines 927 and 932. Mol Cell Biol 23: 402-413
8. Lawrence T, Bebien M, Liu GY, Nizet V, Karin M (2005) IKKα limits macrophage NF-κB activation and contributes to the resolution of inflammation. Nature 434: 1138-1143
9. Li Q, Verma IM (2002) NF-κB regulation in the immune system. Nat Rev Immunol 2: 725-734
10. Maine GN, Mao X, Komarck CM, Burstein E (2007) COMMD1 promotes the ubiquitination of NF-κB subunits through a cullin-containing ubiquitin ligase. EMBO J 26: 436-447
11. Mattioli I, Geng H, Sebald A, Hodel M, Bucher C, Kracht M, Schmitz ML (2006) Inducible phosphorylation of NF-κ B p65 at serine 468 by T cell costimulation is mediated by IKK ζ. J Biol Chem 281: 6175-6183
12. Ravi R, Bedi A, Fuchs EJ (1998) CD95 (Fas)-induced caspase-mediated proteolysis of NF-κB. Cancer Res 58: 882-886
13. Renner F, Schmitz ML (2009) Autoregulatory feedback loops terminating the NF-κB response. Trends Biochem Sci (in press)
14. Ryo A, Suizu F, Yoshida Y, Perrem K, Liou YC, Wulf G, Rottapel R, Yamaoka S, Lu KP (2003) Regulation of NF-κB signaling by Pin1-dependent prolyl isomerization and ubiquitin-mediated proteolysis of p65/RelA. Mol Cell 12: 1413-1426
15. Saccani S, Marazzi I, Beg AA, Natoli G (2004) Degradation of promoter-bound p65/RelA is essential for the prompt termination of the nuclear factor κB response. J Exp Med 200: 107-113
16. Schwabe RF, Sakurai H (2005) IKKβa phosphorylates p65 at S468 in transactivation domain 2. FASEB J 19: 1758-1760
17. Tanaka T, Grusby MJ, Kaisho T (2007) PDLIM2-mediated termination of transcription factor NF-κB activation by intranuclear sequestration and degradation of the p65 subunit. Nat Immunol 8: 584-591
18. Thiefes A, Wolter S, Mushinski JF, Hoffmann E, Dittrich-Breiholz O, Graue N, Dorrie A, Schneider H, Wirth D, Luckow B, Resch K, Kracht M (2005) Simultaneous blockade of NFκB, JNK, and p38 MAPK by a kinase-inactive mutant of the protein kinase TAK1 sensitizes cells to apoptosis and affects a distinct spectrum of tumor necrosis factor [corrected] target genes. J Biol Chem 280: 27728-27741
19. Wietek C, O'Neill LA (2007) Diversity and regulation in the NF-κB system. Trends Biochem Sci 32: 311-319
20. Winzen R, Thakur BK, Dittrich-Breiholz O, Shah M, Redich N, Dhamija S, Kracht M, Holtmann H (2007) Functional analysis of KSRP interaction with the AU-rich element of interleukin-8 and identification of inflammatory mRNA targets. Mol Cell Biol 27: 8388-8400
21. Wolter S, Doerrie A, Weber A, Schneider H, Hoffmann E, von der Ohe J, Bakiri L, Wagner EF, Resch K, Kracht M (2008) c-Jun controls histone modifications, NF-κB recruitment, and RNA polymerase II function to activate the ccl2 gene. Mol Cell Biol 28: 4407-4423
22. Wullaert A, Heyninck K, Janssens S, Beyaert R (2006) Ubiquitin: Tool and target for intracellular NF-κB inhibitors. Trends Immunol 27 533-540
23. Yaron A, Hatzubai A, Davis M, Lavon I, Amit S, Manning AM, Andersen JS, Mann M, Mercurio F, Ben-Neriah Y (1998) Identification of the receptor component of the IκBα-ubiquitin ligase. Nature 396: 590-594
24. Zhong H, Voll RE, Ghosh S (1998) Phosphorylation of NF-κB p65 by PKA stimulates transcriptional activity by promoting a novel bivalent interaction with the coactivator CBP/p300. Mol Cell 1: 661-671