Ser32
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Home > Phosphorylation Site Page: > Ser32  -  IkB-alpha (human)

Site Information
LLDDRHDsGLDsMkD   SwissProt Entrez-Gene
Blast this site against: NCBI  SwissProt  PDB 
Site Group ID: 448203

In vivo Characterization
Methods used to characterize site in vivo:
2D analysis ( 113 ) , [32P] bio-synthetic labeling ( 64 , 70 , 108 , 113 ) , electrophoretic mobility shift ( 71 , 85 , 108 ) , immunoassay ( 28 , 34 ) , immunoprecipitation ( 7 , 8 , 9 , 12 , 32 ) , mass spectrometry ( 13 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 33 , 38 , 43 , 44 , 45 , 46 , 47 ) , mutation of modification site ( 7 , 8 , 10 , 26 , 48 , 58 , 61 , 64 , 70 , 71 , 73 , 75 , 80 , 81 , 82 , 86 , 88 , 94 , 95 , 98 , 99 , 108 , 111 , 112 , 113 ) , peptide sequencing ( 37 ) , phospho-antibody ( 7 , 8 , 9 , 10 , 11 , 12 , 14 , 26 , 27 , 28 , 29 , 30 , 32 , 34 , 35 , 40 , 41 , 42 , 48 , 49 , 50 , 51 , 52 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 83 , 84 , 85 , 86 , 87 , 89 , 90 , 91 , 96 , 97 ) , phosphopeptide mapping ( 108 ) , western blotting ( 7 , 8 , 9 , 10 , 11 , 12 , 14 , 26 , 27 , 29 , 30 , 32 , 35 , 37 , 40 , 41 , 42 , 48 , 49 , 50 , 51 , 52 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 68 , 70 , 72 , 73 , 75 , 77 , 79 , 84 , 86 , 95 , 97 , 111 , 112 )
Disease tissue studied:
bone cancer ( 27 ) , brain cancer ( 29 , 35 ) , glioblastoma ( 29 , 35 ) , glioblastoma multiforme ( 29 ) , glioma ( 29 , 35 ) , HER2 positive breast cancer ( 13 ) , luminal B breast cancer ( 13 ) , cervical cancer ( 40 ) , cervical squamous cell carcinoma ( 40 ) , colorectal cancer ( 11 , 12 , 27 , 42 , 58 , 73 ) , colorectal carcinoma ( 11 , 12 , 27 , 42 , 58 , 73 ) , endometrial cancer ( 61 ) , endometrial adenocarcinoma ( 61 ) , gastric cancer ( 8 , 33 , 47 ) , gastric carcinoma ( 8 , 33 , 47 ) , leukemia ( 11 , 68 , 72 ) , acute myelogenous leukemia ( 68 , 72 ) , T cell leukemia ( 11 ) , liver cancer ( 37 ) , lung cancer ( 9 , 38 , 41 , 43 , 44 , 45 , 46 , 50 , 51 , 60 , 69 ) , non-small cell lung cancer ( 9 , 38 , 43 , 44 , 45 , 46 , 51 ) , non-small cell lung adenocarcinoma ( 38 ) , non-small cell squamous cell lung carcinoma ( 38 ) , lymphoma ( 94 , 96 ) , T cell lymphoma ( 94 ) , ovarian cancer ( 86 ) , multiple myeloma ( 26 )
Relevant cell line - cell type - tissue:
'epithelial, lung' ( 50 ) , 16MB9A (breast cell) ( 83 ) , 267B1 (epithelial) ( 81 ) , 293 (epithelial) [IRAK1 (human)] ( 62 ) , 293 (epithelial) ( 48 , 62 , 73 , 80 ) , 3T3 (fibroblast) [SHP-2 (mouse), homozygous knockout] ( 108 ) , 3T3 (fibroblast) ( 95 ) , A549 (pulmonary) ( 41 , 50 , 51 , 60 , 69 ) , AGS (gastric) ( 8 ) , BAEC (endothelial) ( 52 , 77 ) , blood ( 71 ) , breast ( 13 ) , Caco-2 (intestinal) ( 12 , 58 ) , CCRF-CEM (T lymphocyte) ( 59 ) , cervix ( 74 ) , DU 145 (prostate cell) ( 87 ) , EL-4 (T lymphocyte) [IkB-alpha (human)] ( 113 ) , EL-4 (T lymphocyte) ( 94 ) , endometrium ( 61 ) , endothelial ( 52 ) , fibroblast-skin ( 71 ) , HCT116 (intestinal) ( 27 ) , HEK293T (epithelial) ( 7 , 9 , 71 , 101 ) , HeLa (cervical) ( 27 , 30 , 32 , 48 , 75 , 89 , 97 , 98 , 101 , 108 , 111 ) , HepG2 (hepatic) ( 37 ) , HT-29 (intestinal) ( 11 , 42 , 73 , 90 ) , hTERT-HME1 ( 14 ) , HUVEC (endothelial) ( 49 , 66 ) , Ishikawa (endometrial) ( 61 ) , J774 (macrophage) ( 84 ) , JB (epithelial) ( 63 ) , JPM50.6 (T lymphocyte) ( 57 ) , Jurkat (T lymphocyte) ( 11 , 25 , 55 , 57 , 59 , 70 , 98 , 112 ) , KB (squamous) ( 40 ) , KBM-5 (myeloid) ( 76 ) , LN229 (glial) ( 29 , 64 ) , LNCaP (prostate cell) ( 87 ) , lung ( 43 , 44 , 45 , 46 , 60 ) , M-07e (myeloid) ( 78 ) , M059J (glial) ( 35 ) , M059K (glial) ( 35 ) , MCF-7 (breast cell) ( 83 ) , MEF (fibroblast) ( 52 ) , MEF (fibroblast) [PKR (mouse), homozygous knockout] ( 97 ) , microglia ( 82 ) , MKN-45 (gastric) ( 33 , 47 ) , MM.1R (B lymphocyte) ( 26 ) , MM.1S (lymphoblast) ( 26 ) , monocyte ( 79 , 85 ) , NCI-H1299 (pulmonary) ( 9 , 51 ) , NCI-H1703 (squamous) ( 15 , 38 ) , NCI-H929 (B lymphocyte) ( 26 ) , NCM460 (epithelial) ( 28 , 56 ) , OPM-2 (plasma cell) ( 26 ) , OV2008 (ovarian) ( 86 ) , ovarian ( 32 ) , PC CL 3 (thyroid cell) [TR-beta1 (human), transfection] ( 10 ) , PC3 (prostate cell) ( 65 , 87 ) , RAW 264 (macrophage) ( 72 ) , RPMI-8266 (plasma cell) ( 26 ) , SH-SY5Y (neural crest) ( 64 , 91 ) , T lymphocyte-blood ( 71 ) , T84 (intestinal) ( 58 ) , T98G (glial) ( 29 ) , THP1 (myeloid) ( 68 , 72 ) , U-937 (myeloid) ( 96 , 99 ) , U266 (plasma cell) ( 26 ) , U2OS (bone cell) ( 27 ) , U737 (glial) ( 64 )

Upstream Regulation
Regulatory protein:
AlphaK3 (human) ( 8 ) , Bcl-10 (human) ( 28 ) , CARD11 (human) ( 55 ) , CYBB (human) ( 41 ) , DDX58 (human) ( 41 ) , EGFR (human) ( 14 ) , IkB-alpha (human) ( 67 ) , IKKB (human) ( 61 , 67 ) , IKKG (human) ( 37 ) , LMP1 (herpesvirus) ( 62 ) , MAVS (human) ( 41 ) , MDA5 (human) ( 41 ) , PKR (mouse) ( 97 ) , PLCE1 (human) ( 12 ) , PLK1 (human) ( 48 ) , PRKD2 (human) ( 56 ) , SGK1 (human) ( 67 ) , SHIP (human) ( 59 ) , TIFA (human) ( 8 ) , TR-beta1 (human) ( 10 ) , TRAF2 (human) ( 41 ) , TRAF3 (human) ( 41 ) , TRAF6 (human) ( 41 )
Putative in vivo kinases:
ERK7 (human) ( 9 ) , IKKB (human) ( 98 ) , IKKE (human) ( 98 ) , RSK2 (human) ( 39 )
Kinases, in vitro:
AurC (human) ( 7 ) , CK2A1 (human) ( 99 , 102 ) , ERK7 (human) ( 9 ) , IKKA (human) ( 86 , 93 , 102 , 105 , 106 ) , IKKB (human) ( 54 , 93 , 105 ) , Nik (human) ( 103 ) , p90RSK (human) ( 102 ) , RSK2 (human) ( 39 ) , SGK1 (human) ( 67 )
Treatments:
(5Z)-7-oxozeaenol ( 28 ) , 15d-PGJ2 ( 49 ) , actinomycin_D ( 57 ) , anti-CD28 ( 70 ) , anti-CD3 ( 70 ) , anti-CD3/CD28 ( 57 ) , anti-LT(beta)R ( 73 ) , bacterial infection ( 58 ) , betulinic_acid ( 64 ) , bisindolylmaleimide ( 70 ) , bortezomib ( 61 ) , bradykinin ( 69 ) , cAMP_analog ( 80 ) , carrageenan ( 28 ) , ciclosporin ( 29 ) , cycloheximide ( 57 ) , deferoxamine ( 52 ) , DPI ( 50 ) , EGCG ( 85 ) , EGF ( 53 ) , estradiol ( 68 ) , FeTPPS ( 85 ) , GBS ( 79 ) , gomisin_A ( 30 ) , gomisin_N ( 30 ) , H2O2 ( 59 ) , heregulin ( 83 ) , hypoxia ( 36 ) , hypoxia/reoxygenation ( 75 ) , IGF-1 ( 67 ) , IL-1a ( 89 , 108 ) , IL-1b ( 40 , 58 ) , ionizing_radiation ( 37 ) , ionomycin ( 55 , 94 ) , KP-392 ( 84 ) , LLnL ( 53 , 78 , 96 ) , LPA ( 12 , 56 ) , LPS ( 14 , 72 , 79 , 84 ) , MG132 ( 40 , 57 , 61 , 70 , 80 ) , NAC ( 77 ) , NGF ( 91 ) , nocodazole ( 48 ) , okadaic_acid ( 111 ) , ONOO(-) ( 85 ) , PAR1-activating_peptide ( 42 ) , PAR2-activating_peptide ( 42 ) , parthenolide ( 70 ) , PD98059 ( 79 ) , PEITC ( 65 ) , phorbol_ester ( 55 , 94 , 98 , 99 , 108 , 111 ) , piceatannol ( 76 ) , poly(I-C) ( 97 ) , pomegranate_wine ( 77 ) , SB203580 ( 79 ) , seliciclib ( 51 ) , siRNA ( 50 , 56 , 61 ) , staurosporine ( 68 ) , sulforaphane ( 65 ) , taxol ( 86 ) , tempol ( 28 ) , testosterone ( 68 ) , thrombin ( 60 , 66 ) , TNF ( 8 , 11 , 12 , 30 , 32 , 35 , 39 , 51 , 52 , 53 , 59 , 62 , 63 , 64 , 71 , 73 , 75 , 76 , 77 , 78 , 80 , 83 , 89 , 90 , 91 , 96 , 98 , 99 , 108 , 111 ) , TRAIL ( 11 ) , U0126 ( 63 ) , UV ( 41 , 65 , 75 , 80 ) , vanadate ( 40 , 59 , 75 , 96 ) , virus infection ( 32 , 41 , 50 ) , Z-VAD-FMK ( 11 )

Downstream Regulation
Effects of modification on IkB-alpha:
activity, induced ( 80 , 87 , 88 , 94 ) , intracellular localization ( 9 , 74 ) , molecular association, regulation ( 7 ) , phosphorylation ( 73 ) , protein degradation ( 9 , 39 , 61 , 63 , 64 , 66 , 69 , 71 , 80 , 81 , 84 , 86 , 90 , 94 , 97 , 98 , 106 , 108 , 111 , 112 , 113 )
Effects of modification on biological processes:
apoptosis, altered ( 64 , 87 ) , apoptosis, induced ( 86 ) , apoptosis, inhibited ( 39 , 75 , 88 ) , transcription, altered ( 39 , 71 , 73 , 82 , 87 , 88 , 94 ) , transcription, induced ( 61 , 75 , 111 , 112 )
Induce interaction with:
AurC (human) ( 7 )

Disease / Diagnostics Relevance
Relevant diseases:
HNSCC ( 34 )

References 

1

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2

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3

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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
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6

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7

Han EH, et al. (2017) A small-molecule inhibitor targeting the AURKC-IκBα interaction decreases transformed growth of MDA-MB-231 breast cancer cells. Oncotarget 8, 69691-69708
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8

Zimmermann S, et al. (2017) ALPK1- and TIFA-Dependent Innate Immune Response Triggered by the Helicobacter pylori Type IV Secretion System. Cell Rep 20, 2384-2395
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9

Wu DD, et al. (2017) Extracellular signal-regulated kinase 8-mediated NF-κB activation increases sensitivity of human lung cancer cells to arsenic trioxide. Oncotarget 8, 49144-49155
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10

Park JW, Zhao L, Willingham MC, Cheng SY (2017) Loss of tyrosine phosphorylation at Y406 abrogates the tumor suppressor functions of the thyroid hormone receptor β. Mol Carcinog 56, 489-498
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11

Sosna J, et al. (2016) Differences and Similarities in TRAIL- and Tumor Necrosis Factor-Mediated Necroptotic Signaling in Cancer Cells. Mol Cell Biol 36, 2626-44
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12

Wakita M, et al. (2016) Phospholipase Cϵ Activates Nuclear Factor-κB Signaling by Causing Cytoplasmic Localization of Ribosomal S6 Kinase and Facilitating Its Phosphorylation of Inhibitor κB in Colon Epithelial Cells. J Biol Chem 291, 12586-600
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13

Mertins P, et al. (2016) Proteogenomics connects somatic mutations to signalling in breast cancer. Nature 534, 55-62
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14

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16

Rikova K (2011) CST Curation Set: 13113; Year: 2011; Biosample/Treatment: cell line, MGH-1/unknown; Disease: -; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY])
Curated Info

17

Rikova K (2011) CST Curation Set: 13114; Year: 2011; Biosample/Treatment: cell line, MGH-2/unknown; Disease: -; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY])
Curated Info

18

Rikova K (2011) CST Curation Set: 13115; Year: 2011; Biosample/Treatment: cell line, MGH-3/unknown; Disease: -; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY])
Curated Info

19

Rikova K (2011) CST Curation Set: 13116; Year: 2011; Biosample/Treatment: cell line, MGH-4/unknown; Disease: -; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY])
Curated Info

20

Rikova K (2011) CST Curation Set: 13117; Year: 2011; Biosample/Treatment: cell line, MGH-5/unknown; Disease: -; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY])
Curated Info

21

Rikova K (2011) CST Curation Set: 13118; Year: 2011; Biosample/Treatment: cell line, MGH-6/unknown; Disease: -; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY])
Curated Info

22

Rikova K (2011) CST Curation Set: 13119; Year: 2011; Biosample/Treatment: cell line, MGH-7/unknown; Disease: -; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY])
Curated Info

23

Rikova K (2011) CST Curation Set: 13121; Year: 2011; Biosample/Treatment: cell line, MGH-9/unknown; Disease: -; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY])
Curated Info

24

Rikova K (2011) CST Curation Set: 13122; Year: 2011; Biosample/Treatment: cell line, MGH-10/unknown; Disease: -; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY])
Curated Info

25

Mulhern D (2011) CST Curation Set: 12704; Year: 2011; Biosample/Treatment: cell line, Jurkat/calyculin_A & pervanadate; Disease: T cell leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: DpSG
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26

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
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27

Malik SA, et al. (2011) BH3 mimetics activate multiple pro-autophagic pathways. Oncogene 30, 3918-29
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28

Bhattacharyya S, et al. (2011) Specific effects of BCL10 Serine mutations on phosphorylations in canonical and noncanonical pathways of NF-{kappa}B activation following carrageenan. Am J Physiol Gastrointest Liver Physiol 301, G475-86
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29

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30

Waiwut P, et al. (2011) Gomisin N enhances TNF-α-induced apoptosis via inhibition of the NF-κB and EGFR survival pathways. Mol Cell Biochem 350, 169-75
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31

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
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32

Diel DG, et al. (2011) Orf virus ORFV121 encodes a novel inhibitor of NF-kappaB that contributes to virus virulence. J Virol 85, 2037-49
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33

Guo A (2011) CST Curation Set: 11300; Year: 2011; Biosample/Treatment: cell line, MKN-45/untreated; Disease: gastric carcinoma; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY])
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34

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35

Ju J, et al. (2010) Phosphorylation of p50 NF-kappaB at a single serine residue by DNA-dependent protein kinase is critical for VCAM-1 expression upon TNF treatment. J Biol Chem 285, 41152-60
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36

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37

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38

Moritz A (2010) CST Curation Set: 10594; Year: 2010; Biosample/Treatment: cell line, NCI-H1703/Gleevec; Disease: non-small cell lung cancer; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY]
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39

Peng C, et al. (2010) RSK2 mediates NF-{kappa}B activity through the phosphorylation of IkappaBalpha in the TNF-R1 pathway. FASEB J 24, 3490-9
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40

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41

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42

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43

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Curated Info

44

Rikova K (2010) CST Curation Set: 9764; Year: 2010; Biosample/Treatment: tissue, lung/untreated; Disease: non-small cell lung cancer; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY])
Curated Info

45

Rikova K (2010) CST Curation Set: 9757; Year: 2010; Biosample/Treatment: tissue, lung/untreated; Disease: non-small cell lung cancer; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY])
Curated Info

46

Rikova K (2010) CST Curation Set: 9767; Year: 2010; Biosample/Treatment: tissue, lung/untreated; Disease: non-small cell lung cancer; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY])
Curated Info

47

Moritz A (2010) CST Curation Set: 9234; Year: 2010; Biosample/Treatment: cell line, MKN-45/calyculin_A & pervanadate; Disease: gastric carcinoma; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY])
Curated Info

48

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49

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50

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51

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52

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53

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54

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55

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56

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57

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58

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59

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61

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63

Hu J, Haseebuddin M, Young M, Colburn NH (2005) Suppression of p65 phosphorylation coincides with inhibition of IkappaBalpha polyubiquitination and degradation. Mol Carcinog 44, 274-84
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64

Kasperczyk H, et al. (2005) Betulinic acid as new activator of NF-kappaB: molecular mechanisms and implications for cancer therapy. Oncogene 24, 6945-56
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65

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67

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68

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Chen BC, et al. (2004) Bradykinin B2 receptor mediates NF-kappaB activation and cyclooxygenase-2 expression via the Ras/Raf-1/ERK pathway in human airway epithelial cells. J Immunol 173, 5219-28
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71

Courtois G, et al. (2003) A hypermorphic IkappaBalpha mutation is associated with autosomal dominant anhidrotic ectodermal dysplasia and T cell immunodeficiency. J Clin Invest 112, 1108-15
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72

Yang F, Tang E, Guan K, Wang CY (2003) IKK beta plays an essential role in the phosphorylation of RelA/p65 on serine 536 induced by lipopolysaccharide. J Immunol 170, 5630-5
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73

Jiang X, et al. (2003) The NF-kappa B activation in lymphotoxin beta receptor signaling depends on the phosphorylation of p65 at serine 536. J Biol Chem 278, 919-26
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74

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75

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76

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77

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78

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