Lys310
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Home > Acetylation Site Page: > Lys310  -  NFkB-p65 (human)

Site Information
KRtyEtFksIMkksP   SwissProt Entrez-Gene
Blast this site against: NCBI  SwissProt  PDB 
Site Group ID: 459096

In vivo Characterization
Methods used to characterize site in vivo:
3H acetate labeling ( 34 ) , immunoassay ( 24 ) , immunoprecipitation ( 2 , 8 , 13 , 20 , 24 , 27 , 34 ) , mass spectrometry ( 2 , 23 ) , mass spectrometry (in vitro) ( 27 ) , modification-specific antibody ( 3 , 6 , 8 , 10 , 11 , 12 , 18 , 20 , 24 , 25 , 27 ) , mutation of modification site ( 2 , 10 , 11 , 13 , 20 , 22 , 24 , 25 , 27 , 34 ) , phospho-antibody ( 5 ) , western blotting ( 2 , 3 , 5 , 6 , 8 , 10 , 11 , 12 , 13 , 18 , 20 , 24 , 25 , 27 , 34 )
Disease tissue studied:
bone cancer ( 3 ) , brain cancer ( 11 ) , astrocytoma ( 11 ) , glioblastoma ( 11 ) , glioblastoma multiforme ( 11 ) , glioma ( 11 ) , liver cancer ( 12 ) , hepatocellular carcinoma ( 12 ) , lung cancer ( 3 , 8 , 25 ) , non-small cell lung cancer ( 3 , 8 , 25 ) , non-small cell lung adenocarcinoma ( 8 , 25 ) , melanoma skin cancer ( 24 )
Relevant cell line - cell type - tissue:
293 (epithelial) ( 13 ) , 3T3 (fibroblast) ( 24 , 27 ) , A172 (glial) ( 11 ) , A2058 (keratinocyte) ( 24 ) , A549 (pulmonary) ( 8 , 25 ) , B16 (melanocyte) ( 24 ) , CCF-STTG1 (glial) ( 11 ) , COS7 (fibroblast) ( 34 ) , CRL-1730 (endothelial) ( 18 ) , dendritic cell ( 5 ) , HAEC (endothelial) ( 20 ) , HEK293T (epithelial) ( 2 , 3 , 8 , 10 , 13 , 25 , 27 , 34 ) , HeLa (cervical) ( 34 ) , Hep3B (hepatic) ( 12 ) , HepG2 (hepatic) ( 12 ) , Huh7 (hepatic) ( 12 ) , macrophage-bone marrow ( 6 ) , MEF (fibroblast) ( 10 , 13 , 20 , 22 , 24 , 25 , 34 ) , MV4-11 (macrophage) ( 23 ) , NCI-H1299 (pulmonary) ( 3 ) , T98G (glial) ( 11 ) , U-251 MG (glial) ( 11 ) , U2OS (bone cell) ( 3 ) , U87MG (glial) ( 11 )

Upstream Regulation
Regulatory protein:
ERR1 (human) ( 6 ) , STAT3 (human) ( 24 ) , Tax (retrovirus) ( 10 ) , ZNF366 (human) ( 5 )
Treatments:
AGK2 ( 11 ) , AK1 ( 11 ) , IL-10 ( 24 ) , LPS ( 6 ) , MS275 ( 23 ) , nicotinamide ( 18 , 27 ) , resveratrol ( 18 , 20 ) , selisistat ( 12 ) , siRNA ( 3 , 11 , 12 , 13 , 18 , 20 ) , splitomicin ( 20 ) , TNF ( 3 , 24 , 27 ) , trichostatin_A ( 13 , 18 , 24 , 27 )

Downstream Regulation
Effects of modification on NFkB-p65:
activity, induced ( 10 , 25 ) , intracellular localization ( 24 ) , molecular association, regulation ( 8 , 10 , 11 , 25 )
Effects of modification on biological processes:
apoptosis, inhibited ( 11 ) , carcinogenesis, induced ( 11 , 12 , 24 ) , cell growth, induced ( 11 , 12 ) , signaling pathway regulation ( 6 ) , transcription, altered ( 27 ) , transcription, induced ( 3 , 11 , 12 , 18 , 20 , 22 , 24 , 25 , 34 ) , transcription, inhibited ( 2 ) , translation, induced ( 18 )
Induce interaction with:
BRD4 (human) ( 8 , 10 , 25 ) , DNA ( 11 , 25 )

Disease / Diagnostics Relevance
Relevant diseases:
lung cancer ( 24 )

References 

1

Shahbazi S, Zakerali T, Frycz B, Kaur J (2020) Impact of novel N-aryl substituted piperamide on NF-kappa B translocation as a potent anti-neuroinflammatory agent. Biomed Pharmacother 127, 110199
32416562   Curated Info

2

Ma Z, Chalkley RJ, Vosseller K (2017) Hyper-O-GlcNAcylation activates nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) signaling through interplay with phosphorylation and acetylation. J Biol Chem 292, 9150-9163
28416608   Curated Info

3

Li Z, et al. (2016) USP4 inhibits p53 and NF-κB through deubiquitinating and stabilizing HDAC2. Oncogene 35, 2902-12
26411366   Curated Info

4

Fischer N, et al. (2016) Histone deacetylase inhibition enhances antimicrobial peptide but not inflammatory cytokine expression upon bacterial challenge. Proc Natl Acad Sci U S A 113, E2993-3001
27162363   Curated Info

5

Søndergaard JN, et al. (2015) DC-SCRIPT Regulates IL-10 Production in Human Dendritic Cells by Modulating NF-κBp65 Activation. J Immunol 195, 1498-505
26170389   Curated Info

6

Yuk JM, et al. (2015) Orphan Nuclear Receptor ERRα Controls Macrophage Metabolic Signaling and A20 Expression to Negatively Regulate TLR-Induced Inflammation. Immunity 43, 80-91
26200012   Curated Info

7

Kühnemuth B, et al. (2015) CUX1 modulates polarization of tumor-associated macrophages by antagonizing NF-κB signaling. Oncogene 34, 177-87
24336331   Curated Info

8

Zou Z, et al. (2014) Brd4 maintains constitutively active NF-κB in cancer cells by binding to acetylated RelA. Oncogene 33, 2395-404
23686307   Curated Info

9

Sgarbanti M, et al. (2014) IκB Kinase {varepsilon} Targets Interferon Regulatory Factor 1 in Activated T Lymphocytes. Mol Cell Biol 34, 1054-65
24396068   Curated Info

10

Wu X, et al. (2013) Bromodomain and extraterminal (BET) protein inhibition suppresses human T cell leukemia virus 1 (HTLV-1) Tax protein-mediated tumorigenesis by inhibiting nuclear factor κB (NF-κB) signaling. J Biol Chem 288, 36094-105
24189064   Curated Info

11

Li Y, et al. (2013) Sirt2 suppresses glioma cell growth through targeting NF-κB-miR-21 axis. Biochem Biophys Res Commun 441, 661-7
24161395   Curated Info

12

Gang D, et al. (2013) The tumor suppressor protein menin inhibits NF-κB-mediated transactivation through recruitment of Sirt1 in hepatocellular carcinoma. Mol Biol Rep 40, 2461-6
23224434   Curated Info

13

Ziesché E, et al. (2013) The coactivator role of histone deacetylase 3 in IL-1-signaling involves deacetylation of p65 NF-κB. Nucleic Acids Res 41, 90-109
23087373   Curated Info

14

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

15

Allison DF, et al. (2012) Modification of RelA by O-linked N-acetylglucosamine links glucose metabolism to NF-κB acetylation and transcription. Proc Natl Acad Sci U S A 109, 16888-93
23027940   Curated Info

16

Beli P, et al. (2012) Proteomic Investigations Reveal a Role for RNA Processing Factor THRAP3 in the DNA Damage Response. Mol Cell 46, 212-25
22424773   Curated Info

17

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

18

Yang L, et al. (2012) SIRT1 Regulates CD40 Expression Induced by TNF-α via NF-ĸB Pathway in Endothelial Cells. Cell Physiol Biochem 30, 1287-98
23075766   Curated Info

19

Zhang Y, et al. (2011) AMP-activated protein kinase suppresses endothelial cell inflammation through phosphorylation of transcriptional coactivator p300. Arterioscler Thromb Vasc Biol 31, 2897-908
21940946   Curated Info

20

Breitenstein A, et al. (2011) Sirt1 inhibition promotes in vivo arterial thrombosis and tissue factor expression in stimulated cells. Cardiovasc Res 89, 464-72
20978007   Curated Info

21

Yang XD, Tajkhorshid E, Chen LF (2010) Functional interplay between acetylation and methylation of the RelA subunit of NF-kappaB. Mol Cell Biol 30, 2170-80
20160011   Curated Info

22

Rothgiesser KM, Fey M, Hottiger MO (2010) Acetylation of p65 at lysine 314 is important for late NF-kappaB-dependent gene expression. BMC Genomics 11, 22
20064247   Curated Info

23

Choudhary C, et al. (2009) Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science 325, 834-40
19608861   Curated Info

24

Lee H, et al. (2009) Persistently activated Stat3 maintains constitutive NF-kappaB activity in tumors. Cancer Cell 15, 283-93
19345327   Curated Info

25

Huang B, et al. (2009) Brd4 coactivates transcriptional activation of NF-kappaB via specific binding to acetylated RelA. Mol Cell Biol 29, 1375-87
19103749   Curated Info

26

Choi KC, et al. (2009) Epigallocatechin-3-gallate, a histone acetyltransferase inhibitor, inhibits EBV-induced B lymphocyte transformation via suppression of RelA acetylation. Cancer Res 69, 583-92
19147572   Curated Info

27

Buerki C, et al. (2008) Functional relevance of novel p300-mediated lysine 314 and 315 acetylation of RelA/p65. Nucleic Acids Res 36, 1665-80
18263619   Curated Info

28

Dai Y, et al. (2008) Interactions between Bortezomib and Romidepsin and Belinostat in Chronic Lymphocytic Leukemia Cells. Clin Cancer Res 14, 549-58
18223231   Curated Info

29

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

30

Singh M, Popowicz GM, Krajewski M, Holak TA (2007) Structural ramification for acetyl-lysine recognition by the bromodomain of human BRG1 protein, a central ATPase of the SWI/SNF remodeling complex. Chembiochem 8, 1308-16
17582821   Curated Info

31

Ito K (2007) Impact of post-translational modifications of proteins on the inflammatory process. Biochem Soc Trans 35, 281-3
17371260   Curated Info

32

Liu Y, et al. (2006) Suberoylanilide hydroxamic acid induces Akt-mediated phosphorylation of p300, which promotes acetylation and transcriptional activation of RelA/p65. J Biol Chem 281, 31359-68
16926151   Curated Info

33

Yeung F, et al. (2004) Modulation of NF-kappaB-dependent transcription and cell survival by the SIRT1 deacetylase. EMBO J 23, 2369-80
15152190   Curated Info

34

Chen LF, Mu Y, Greene WC (2002) Acetylation of RelA at discrete sites regulates distinct nuclear functions of NF-kappaB. EMBO J 21, 6539-48
12456660   Curated Info