Ser468
Javascript is not enabled on this browser. This site will not work properly without Javascript.
PhosphoSitePlus Homepage PhosphoSitePlus® v6.5.9.3
Powered by Cell Signaling Technology
Home > Phosphorylation Site Page: > Ser468  -  NFkB-p65 (human)

Site Information
AVFTDLAsVDNsEFQ   SwissProt Entrez-Gene
Blast this site against: NCBI  SwissProt  PDB 
Site Group ID: 451145

In vivo Characterization
Methods used to characterize site in vivo:
electrophoretic mobility shift ( 12 ) , immunoprecipitation ( 7 ) , mutation of modification site ( 7 , 9 , 10 , 12 ) , phospho-antibody ( 2 , 3 , 5 , 7 , 8 , 9 , 10 , 11 , 12 , 13 ) , western blotting ( 2 , 3 , 5 , 7 , 8 , 9 , 10 , 12 )
Disease tissue studied:
brain cancer ( 10 ) , glioblastoma ( 10 ) , glioma ( 10 ) , breast cancer ( 10 ) , liver cancer ( 10 ) , lymphoma ( 10 ) , B cell lymphoma ( 10 ) , multiple myeloma ( 3 )
Relevant cell line - cell type - tissue:
293 (epithelial) ( 7 ) , HEK293T (epithelial) ( 2 ) , HeLa (cervical) ( 5 , 10 , 12 ) , Hep 3B2.1-7 (hepatic) ( 10 ) , hepatocyte-liver ( 10 ) , HKC (epithelial) ( 8 ) , Jurkat (T lymphocyte) ( 9 , 10 , 11 ) , MCF-7 (breast cell) ( 10 ) , MEF (fibroblast) ( 7 , 9 , 10 ) , MEF (fibroblast) [NFkB-p65 (mouse), homozygous knockout] ( 5 , 7 ) , MM.1R (B lymphocyte) ( 3 ) , MM.1S (lymphoblast) ( 3 ) , NCI-H929 (B lymphocyte) ( 3 ) , OPM-2 (plasma cell) ( 3 ) , RPMI-8266 (plasma cell) ( 3 ) , SKW 6.4 (B lymphocyte) ( 10 ) , T lymphocyte-blood ( 11 , 13 ) , U-251 MG (glial) ( 10 ) , U266 (plasma cell) ( 3 ) , U373 MG (glial) ( 11 )

Upstream Regulation
Regulatory protein:
CK1G1 (human) ( 2 ) , GSK3B (human) ( 8 )
Putative in vivo kinases:
GSK3B (human) ( 8 , 12 ) , IKKB (human) ( 10 ) , IKKE (human) ( 5 , 9 )
Kinases, in vitro:
GSK3B (human) ( 8 , 12 ) , IKKB (human) ( 10 ) , IKKE (human) ( 9 )
Treatments:
anti-CD3/CD28 ( 13 ) , anti-CD43 ( 13 ) , calyculin_A ( 10 , 12 ) , GSK-3_inhibitor_I ( 10 ) , HGF ( 8 ) , IL-1b ( 10 ) , ionomycin ( 9 ) , LBH-589 ( 3 ) , lithium ( 9 , 12 ) , LY294002 ( 10 ) , PD98059 ( 10 ) , phorbol_ester ( 9 , 10 ) , PS-1145 ( 10 ) , S-valproate ( 8 ) , SB203580 ( 10 ) , siRNA ( 8 , 9 ) , SP600125 ( 10 ) , TNF ( 8 , 10 , 11 ) , virus infection ( 2 ) , vorinostat ( 3 )

Downstream Regulation
Effects of modification on NFkB-p65:
activity, induced ( 8 , 9 ) , activity, inhibited ( 12 ) , intracellular localization ( 5 ) , protein degradation ( 7 ) , ubiquitination ( 7 )
Effects of modification on biological processes:
transcription, altered ( 5 , 10 , 12 ) , transcription, induced ( 8 , 9 ) , transcription, inhibited ( 7 )
Induce interaction with:
COMMD1 (human) ( 7 ) , CUL2 (human) ( 7 )

References 

1

Kolesnichenko M, et al. (2021) Transcriptional repression of NFKBIA triggers constitutive IKK- and proteasome-independent p65/RelA activation in senescence. EMBO J, e104296
33459422   Curated Info

2

Wang Y, Hu L, Tong X, Ye X (2014) Casein Kinase 1γ1 Inhibits the RIG-I/TLR Signaling Pathway through Phosphorylating p65 and Promoting Its Degradation. J Immunol 192, 1855-61
24442433   Curated Info

3

Dai Y, et al. (2011) Disruption of IkappaB kinase (IKK)-mediated RelA serine 536 phosphorylation sensitizes human multiple myeloma cells to histone deacetylase (HDAC) inhibitors. J Biol Chem 286, 34036-50
21816815   Curated Info

4

Guitton C, et al. (2011) Protective cross talk between activated protein C and TNF signaling in vascular endothelial cells: implication of EPCR, noncanonical NF-κB, and ERK1/2 MAP kinases. Am J Physiol Cell Physiol 300, C833-42
21228323   Curated Info

5

Moreno R, Sobotzik JM, Schultz C, Schmitz ML (2010) Specification of the NF-kappaB transcriptional response by p65 phosphorylation and TNF-induced nuclear translocation of IKK epsilon. Nucleic Acids Res 38, 6029-44
20507904   Curated Info

6

Renner F, Moreno R, Schmitz ML (2010) SUMOylation-dependent localization of IKKepsilon in PML nuclear bodies is essential for protection against DNA-damage-triggered cell death. Mol Cell 37, 503-15
20188669   Curated Info

7

Geng H, et al. (2009) Phosphorylation of NF-kappaB p65 at Ser468 controls its COMMD1-dependent ubiquitination and target gene-specific proteasomal elimination. EMBO Rep 10, 381-6
19270718   Curated Info

8

Gong R, et al. (2008) Hepatocyte growth factor suppresses proinflammatory NFkappaB activation through GSK3beta inactivation in renal tubular epithelial cells. J Biol Chem 283, 7401-10
18201972   Curated Info

9

Mattioli I, et al. (2006) Inducible phosphorylation of NF-kappa B p65 at serine 468 by T cell costimulation is mediated by IKK epsilon. J Biol Chem 281, 6175-83
16407239   Curated Info

10

Schwabe RF, Sakurai H (2005) IKKbeta phosphorylates p65 at S468 in transactivaton domain 2. FASEB J 19, 1758-60
16046471   Curated Info

11

Sancho R, et al. (2005) Mechanisms of HIV-1 inhibition by the lipid mediator N-arachidonoyldopamine. J Immunol 175, 3990-9
16148147   Curated Info

12

Buss H, et al. (2004) Phosphorylation of serine 468 by GSK-3beta negatively regulates basal p65 NF-kappaB activity. J Biol Chem 279, 49571-4
15465828   Curated Info

13

Mattioli I, et al. (2004) Comparative analysis of T-cell costimulation and CD43 activation reveals novel signaling pathways and target genes. Blood 104, 3302-4
15280197   Curated Info