Ser276
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Home > Phosphorylation Site Page: > Ser276  -  NFkB-p65 (human)

Site Information
sMQLRRPsDRELsEP   SwissProt Entrez-Gene
Blast this site against: NCBI  SwissProt  PDB 
Site Group ID: 447798

In vivo Characterization
Methods used to characterize site in vivo:
2D analysis ( 42 ) , immunoassay ( 3 ) , immunoprecipitation ( 15 , 16 , 20 , 21 , 23 , 25 , 46 , 47 ) , mutation of modification site ( 7 , 15 , 21 , 24 , 25 , 30 , 31 , 37 , 39 , 42 , 43 , 44 , 45 , 46 , 47 ) , phospho-antibody ( 1 , 3 , 4 , 5 , 6 , 11 , 13 , 15 , 16 , 17 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 28 , 29 , 33 , 34 , 35 , 36 , 38 , 40 , 41 , 43 ) , western blotting ( 1 , 3 , 4 , 5 , 6 , 11 , 13 , 15 , 16 , 17 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 28 , 29 , 33 , 34 , 35 , 36 , 38 , 40 , 43 , 47 )
Disease tissue studied:
breast cancer ( 16 , 22 ) , cervical cancer ( 25 ) , cervical adenocarcinoma ( 25 ) , colorectal cancer ( 19 ) , colorectal carcinoma ( 19 ) , leukemia ( 5 , 39 ) , acute myelogenous leukemia ( 39 ) , T cell leukemia ( 5 ) , liver cancer ( 1 ) , hepatocellular carcinoma ( 1 ) , lung cancer ( 24 , 25 , 28 , 38 ) , non-small cell lung cancer ( 24 , 28 ) , lymphoma ( 5 ) , Hodgkin's lymphoma ( 5 )
Relevant cell line - cell type - tissue:
293 (epithelial) ( 16 , 37 , 43 , 46 ) , 3T3 (fibroblast) ( 7 ) , A549 (pulmonary) ( 25 , 28 , 38 ) , BAEC (endothelial) ( 30 ) , bEnd3 ( 7 ) , COS (fibroblast) ( 21 , 45 , 47 ) , CV1 (fibroblast) ( 40 , 46 ) , D425 ( 13 ) , dendritic cell ( 20 ) , endothelial-aorta ( 42 ) , fibroblast-lung ( 23 ) , HCCLM3 (hepatic) ( 1 ) , HDLM-2 (lymphoid) ( 5 ) , heart ( 11 ) , HEK293T (epithelial) ( 15 ) , HeLa (cervical) ( 21 , 36 ) , HeLa S3 (cervical) ( 25 ) , HepG2 (hepatic) ( 1 ) , HT-29 (intestinal) ( 19 ) , Jurkat (T lymphocyte) ( 5 , 41 , 44 , 47 ) , KAd5 ( 29 ) , keratinocyte-skin ( 34 ) , KM-H2 (lymphoid) ( 5 ) , L1236 (lymphoid) ( 5 ) , L428 (lymphoid) ( 5 ) , L540 (lymphoid) ( 5 ) , L929 (fibroblast) ( 43 ) , MDA-MB-231 (breast cell) ( 16 , 22 ) , MEF (fibroblast) ( 25 , 31 , 42 ) , microglia ( 3 ) , monocyte ( 35 ) , myocyte-heart ( 11 ) , NCI-H1299 (pulmonary) ( 28 ) , NCI-H460 (pulmonary) ( 24 ) , peritoneum ( 4 ) , preadipocyte ( 4 ) , QSG7701 (hepatocyte) ( 1 ) , T lymphocyte-blood ( 41 ) , T/C-28a2 (chondrocyte) ( 17 ) , THP1 (myeloid) ( 39 ) , U2OS (bone cell) ( 33 ) , U373 MG (glial) ( 41 )

Upstream Regulation
Regulatory protein:
AKIP (human) ( 16 ) , CDK5RAP3 (human) ( 33 ) , DAXX (human) ( 36 ) , GSK3B (human) ( 26 ) , Pim1 (human) ( 5 ) , Pim2 (human) ( 5 ) , PTGER2 (mouse) ( 17 ) , PTGER3 (mouse) ( 17 ) , SPARC (human) ( 4 ) , TLR3 (human) ( 38 )
Putative in vivo kinases:
MSK1 (human) ( 1 , 8 , 23 , 43 ) , MSK2 (human) ( 22 ) , p90RSK (human) ( 19 ) , Pim1 (human) ( 21 ) , PKACA (human) ( 16 , 29 , 47 ) , RSK2 (human) ( 19 )
Kinases, in vitro:
MSK1 (human) ( 43 ) , Pim1 (human) ( 21 ) , PKACA (human) ( 18 , 27 , 29 , 45 ) , PKACA (mouse) ( 15 )
Treatments:
AH6809 ( 17 ) , cAMP_analog ( 16 ) , CDDO-Me ( 3 ) , dimethylfumarate ( 34 ) , DMAT ( 22 ) , DMSO ( 25 ) , double-stranded_RNA ( 37 ) , EGF ( 1 ) , ethanol ( 35 ) , farnesol ( 8 , 24 ) , fluid_shear_stress ( 17 ) , fumaric_acid ( 34 ) , GW_5074 ( 20 ) , H-89 ( 1 , 17 , 19 , 22 , 23 , 29 , 43 ) , HGF ( 26 ) , IL-1b ( 23 , 34 ) , LPS ( 35 ) , LY294002 ( 17 ) , methylhydrogenfumarate ( 34 ) , NAC ( 25 ) , NS398 ( 17 ) , PAR1-activating_peptide ( 19 ) , PAR2-activating_peptide ( 19 ) , PD98059 ( 19 , 23 ) , S-valproate ( 26 ) , SB202190 ( 23 ) , SB203580 ( 22 , 40 ) , SEL24-B489 ( 5 ) , seliciclib ( 28 ) , siRNA ( 19 , 26 , 38 ) , SL0101 ( 19 ) , SP600125 ( 40 ) , status epilepticus ( 3 ) , sulprostone ( 17 ) , TAK1_inhibitor ( 6 ) , TNF ( 8 , 16 , 21 , 25 , 26 , 28 , 33 , 36 , 41 , 43 ) , U0126 ( 40 ) , UV ( 22 ) , virus infection ( 20 , 40 ) , wortmannin ( 17 )

Downstream Regulation
Effects of modification on NFkB-p65:
acetylation ( 8 ) , activity, induced ( 22 , 38 , 39 , 43 ) , intracellular localization ( 7 , 31 ) , molecular association, regulation ( 7 , 9 , 15 , 20 , 23 , 39 , 45 , 46 , 47 ) , phosphorylation ( 3 ) , protein stabilization ( 21 )
Effects of modification on biological processes:
apoptosis, inhibited ( 21 ) , signaling pathway regulation ( 3 ) , transcription, altered ( 21 , 22 , 23 , 24 , 29 , 31 , 42 , 43 ) , transcription, induced ( 1 , 7 , 15 , 16 , 19 , 20 , 25 , 30 , 38 , 47 ) , transcription, inhibited ( 9 , 46 )
Induce interaction with:
CBP (human) ( 23 , 45 , 47 ) , DNA ( 7 , 39 ) , DNMT1 (human) ( 9 ) , PKACA (human) ( 46 ) , eEF1B (human) ( 20 ) , p300 (human) ( 15 )
Inhibit interaction with:
HDAC1 (human) ( 45 )

References 

1

Chen H, et al. (2021) Epidermal growth factor upregulates the expression of A20 in hepatic cells via the MEK1/MSK1/p-p65 (Ser276) signaling pathway. Am J Transl Res 13, 708-718
33594320   Curated Info

2

Lim SG, Suk K, Lee WH (2020) LETMD1 Regulates Phagocytosis and Inflammatory Responses to Lipopolysaccharide via Reactive Oxygen Species Generation and NF-¿¿B Activation in Macrophages. J Immunol
31980577   Curated Info

3

Kim MJ, et al. (2019) CDDO-Me Attenuates Vasogenic Edema and Astroglial Death by Regulating NF-κB p65 Phosphorylations and Nrf2 Expression Following Status Epilepticus. Int J Mol Sci 20
31574956   Curated Info

4

John B, et al. (2019) Regulation of the bi-directional cross-talk between ovarian cancer cells and adipocytes by SPARC. Oncogene
30765860   Curated Info

5

Szydłowski M, et al. (2017) Expression of PIM kinases in Reed-Sternberg cells fosters immune privilege and tumor cell survival in Hodgkin lymphoma. Blood 130, 1418-1429
28698206   Curated Info

6

Huang HL, Chiang CH, Hung WC, Hou MF (2015) Targeting of TGF-β-activated protein kinase 1 inhibits chemokine (C-C motif) receptor 7 expression, tumor growth and metastasis in breast cancer. Oncotarget 6, 995-1007
25557171   Curated Info

7

Hochrainer K, Racchumi G, Anrather J (2013) Site-specific phosphorylation of the p65 protein subunit mediates selective gene expression by differential NF-κB and RNA polymerase II promoter recruitment. J Biol Chem 288, 285-93
23100252   Curated Info

8

Ning Z, et al. (2013) The N terminus of orf virus-encoded protein 002 inhibits acetylation of NF-κB p65 by preventing Ser(276) phosphorylation. PLoS One 8, e58854
23536830   Curated Info

9

Liu Y, et al. (2012) Phosphorylation of RelA/p65 promotes DNMT-1 recruitment to chromatin and represses transcription of the tumor metastasis suppressor gene BRMS1. Oncogene 31, 1143-54
21765477   Curated Info

10

Clavijo PE, Frauwirth KA (2012) Anergic CD8+ T lymphocytes have impaired NF-κB activation with defects in p65 phosphorylation and acetylation. J Immunol 188, 1213-21
22205033   Curated Info

11

Gu Q, et al. (2011) Hypoxia-induced SOCS3 is limiting STAT3 phosphorylation and NF-κB activation in congenital heart disease. Biochimie 93, 909-20
21354254   Curated Info

12

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

13

Spiller SE, Logsdon NJ, Deckard LA, Sontheimer H (2011) Inhibition of nuclear factor kappa-B signaling reduces growth in medulloblastoma in vivo. BMC Cancer 11, 136
21492457   Curated Info

14

Bao X, et al. (2010) IKKε modulates RSV-induced NF-κB-dependent gene transcription. Virology 408, 224-31
20961594   Curated Info

15

Tago K, et al. (2010) KappaB-Ras is a nuclear-cytoplasmic small GTPase that inhibits NF-kappaB activation through the suppression of transcriptional activation of p65/RelA. J Biol Chem 285, 30622-33
20639196   Curated Info

16

Gao N, et al. (2010) A-kinase-interacting protein 1 (AKIP1) acts as a molecular determinant of PKA in NF-kappaB signaling. J Biol Chem 285, 28097-104
20562110   Curated Info

17

Wang P, Zhu F, Lee NH, Konstantopoulos K (2010) Shear-induced interleukin-6 synthesis in chondrocytes: roles of E prostanoid (EP) 2 and EP3 in cAMP/protein kinase A- and PI3-K/Akt-dependent NF-kappaB activation. J Biol Chem 285, 24793-804
20516073   Curated Info

18

Jiao J, Guan H, Lippa AM, Ricciardi RP (2010) The N terminus of adenovirus type 12 E1A inhibits major histocompatibility complex class I expression by preventing phosphorylation of NF-kappaB p65 Ser276 through direct binding. J Virol 84, 7668-74
20504937   Curated Info

19

Wang H, Moreau F, Hirota CL, MacNaughton WK (2010) Proteinase-activated receptors induce interleukin-8 expression by intestinal epithelial cells through ERK/RSK90 activation and histone acetylation. FASEB J 24, 1971-80
20065107   Curated Info

20

Gringhuis SI, et al. (2010) HIV-1 exploits innate signaling by TLR8 and DC-SIGN for productive infection of dendritic cells. Nat Immunol 11, 419-26
20364151   Curated Info

21

Nihira K, et al. (2010) Pim-1 controls NF-kappaB signalling by stabilizing RelA/p65. Cell Death Differ 17, 689-98
19911008   Curated Info

22

Jacks KA, Koch CA (2010) Differential regulation of mitogen- and stress-activated protein kinase-1 and -2 (MSK1 and MSK2) by CK2 following UV radiation. J Biol Chem 285, 1661-70
19933278   Curated Info

23

Reber L, Vermeulen L, Haegeman G, Frossard N (2009) Ser276 phosphorylation of NF-kB p65 by MSK1 controls SCF expression in inflammation. PLoS One 4, e4393
19197368   Curated Info

24

Joo JH, Jetten AM (2008) NF-kappaB-dependent transcriptional activation in lung carcinoma cells by farnesol involves p65/RelA(Ser276) phosphorylation via the MEK-MSK1 signaling pathway. J Biol Chem 283, 16391-9
18424438   Curated Info

25

Nowak DE, et al. (2008) RelA Ser276 phosphorylation is required for activation of a subset of NF-kappaB-dependent genes by recruiting cyclin-dependent kinase 9/cyclin T1 complexes. Mol Cell Biol 28, 3623-38
18362169   Curated Info

26

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

27

Gao N, et al. (2008) AKIP1 enhances NF-kappaB-dependent gene expression by promoting the nuclear retention and phosphorylation of p65. J Biol Chem 283, 7834-43
18178962   Curated Info

28

Dey A, et al. (2008) R-Roscovitine simultaneously targets both the p53 and NF-kappaB pathways and causes potentiation of apoptosis: implications in cancer therapy. Cell Death Differ 15, 263-73
17975552   Curated Info

29

Guan H, Jiao J, Ricciardi RP (2008) Tumorigenic adenovirus type 12 E1A inhibits phosphorylation of NF-kappaB by PKAc, causing loss of DNA binding and transactivation. J Virol 82, 40-8
17959673   Curated Info

30

Seldon MP, et al. (2007) Heme oxygenase-1 inhibits the expression of adhesion molecules associated with endothelial cell activation via inhibition of NF-kappaB RelA phosphorylation at serine 276. J Immunol 179, 7840-51
18025230   Curated Info

31

Hochrainer K, Racchumi G, Anrather J (2007) Hypo-phosphorylation leads to nuclear retention of NF-kappaB p65 due to impaired IkappaBalpha gene synthesis. FEBS Lett 581, 5493-9
17991436   Curated Info

32

Saha RN, Jana M, Pahan K (2007) MAPK p38 regulates transcriptional activity of NF-kappaB in primary human astrocytes via acetylation of p65. J Immunol 179, 7101-9
17982102   Curated Info

33

Wang J, et al. (2007) LZAP, a putative tumor suppressor, selectively inhibits NF-kappaB. Cancer Cell 12, 239-51
17785205   Curated Info

34

Gesser B, et al. (2007) Dimethylfumarate specifically inhibits the mitogen and stress-activated kinases 1 and 2 (MSK1/2): possible role for its anti-psoriatic effect. J Invest Dermatol 127, 2129-37
17495961   Curated Info

35

Mandrekar P, Jeliazkova V, Catalano D, Szabo G (2007) Acute alcohol exposure exerts anti-inflammatory effects by inhibiting IkappaB kinase activity and p65 phosphorylation in human monocytes. J Immunol 178, 7686-93
17548605   Curated Info

36

Park J, et al. (2007) Inhibition of NF-kappaB acetylation and its transcriptional activity by Daxx. J Mol Biol 368, 388-97
17362989   Curated Info

37

Sarkar SN, et al. (2007) Two tyrosine residues of Toll-like receptor 3 trigger different steps of NF-kappa B activation. J Biol Chem 282, 3423-7
17178723   Curated Info

38

Liu P, et al. (2007) Retinoic acid-inducible gene I mediates early antiviral response and Toll-like receptor 3 expression in respiratory syncytial virus-infected airway epithelial cells. J Virol 81, 1401-11
17108032   Curated Info

39

Pathak SK, et al. (2006) TLR4-dependent NF-kappaB activation and mitogen- and stress-activated protein kinase 1-triggered phosphorylation events are central to Helicobacter pylori peptidyl prolyl cis-, trans-isomerase (HP0175)-mediated induction of IL-6 release from macrophages. J Immunol 177, 7950-8
17114467   Curated Info

40

Hargett D, Rice S, Bachenheimer SL (2006) Herpes simplex virus type 1 ICP27-dependent activation of NF-kappaB. J Virol 80, 10565-78
16928747   Curated Info

41

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

42

Anrather J, Racchumi G, Iadecola C (2005) cis-acting, element-specific transcriptional activity of differentially phosphorylated nuclear factor-kappa B. J Biol Chem 280, 244-52
15516339   Curated Info

43

Vermeulen L, et al. (2003) Transcriptional activation of the NF-kappaB p65 subunit by mitogen- and stress-activated protein kinase-1 (MSK1). EMBO J 22, 1313-24
12628924   Curated Info

44

Takahashi N, Tetsuka T, Uranishi H, Okamoto T (2002) Inhibition of the NF-kappaB transcriptional activity by protein kinase A. Eur J Biochem 269, 4559-65
12230568   Curated Info

45

Zhong H, May MJ, Jimi E, Ghosh S (2002) The phosphorylation status of nuclear NF-kappa B determines its association with CBP/p300 or HDAC-1. Mol Cell 9, 625-36
11931769   Curated Info

46

Doucas V, et al. (2000) Cytoplasmic catalytic subunit of protein kinase A mediates cross-repression by NF-kappa B and the glucocorticoid receptor. Proc Natl Acad Sci U S A 97, 11893-8
11027313   Curated Info

47

Zhong H, Voll RE, Ghosh S (1998) Phosphorylation of NF-kappa B p65 by PKA stimulates transcriptional activity by promoting a novel bivalent interaction with the coactivator CBP/p300. Mol Cell 1, 661-71
9660950   Curated Info