Negative regulation of RelA phosphorylation: Emerging players and their roles in cancer

Cytokine and Growth Factor Reviews

Volumn 26, Issue 1, 2015, Pages 7-13

  Lu, Xinyuan ^a,b   Yarbrough, Wendell G ^c,d  

^a VANDERBILT UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

^c YALE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^d YALE CANCER CENTER   (United States)

Author keywords

LZAP; NF B; Phosphatase; PPM1A; Tumor suppressor

Indexed keywords

IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; PHOSPHOPROTEIN PHOSPHATASE; PHOSPHOPROTEIN PHOSPHATASE 2A; SERINE; SERINE THREONINE PHOSPHATASE; TRANSCRIPTION FACTOR RELA; UNCLASSIFIED DRUG; CDK5RAP3 PROTEIN, HUMAN; NERVE PROTEIN; PHOSPHATASE; RELA PROTEIN, HUMAN; SIGNAL PEPTIDE;

CANCER INHIBITION; CARCINOGENESIS; CELL PROLIFERATION; ENZYME ACTIVITY; FRAMESHIFT MUTATION; GENE DELETION; HUMAN; MALIGNANT NEOPLASTIC DISEASE; NONHUMAN; PROTEIN FUNCTION; PROTEIN PHOSPHORYLATION; PROTEIN PROCESSING; PROTEIN TARGETING; SHORT SURVEY; SIGNAL TRANSDUCTION; GENE EXPRESSION REGULATION; GENETICS; METABOLISM; NEOPLASM; PATHOPHYSIOLOGY; PHOSPHORYLATION;

GENE EXPRESSION REGULATION, NEOPLASTIC; HUMANS; INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS; NEOPLASMS; NERVE TISSUE PROTEINS; PHOSPHORIC MONOESTER HYDROLASES; PHOSPHORYLATION; PROTEIN PROCESSING, POST-TRANSLATIONAL; SIGNAL TRANSDUCTION; TRANSCRIPTION FACTOR RELA;

EID: 84922919150     PISSN: 13596101     EISSN: 18790305     Source Type: Journal    
DOI: 10.1016/j.cytogfr.2014.09.003     Document Type: Short Survey

References (84)

1. Sen R., Baltimore D. Multiple nuclear factors interact with the immunoglobulin enhancer sequences. Cell 1986, 46:705-716.
2. Chen L.F., Greene W.C. Shaping the nuclear action of NF-kappaB. Nat Rev Mol Cell Biol 2004, 5(5):392-401.
3. Vermeulen L., De Wilde G., Van Damme P., Vanden Berghe W., Haegeman G. Transcriptional activation of the NF-kappaB p65 subunit by mitogen- and stress-activated protein kinase-1 (MSK1). EMBO J 2003, 22(6):1313-1324.
4. Viatour P., Merville M.P., Bours V., Chariot A. Phosphorylation of NF-kappaB and IkappaB proteins: implications in cancer and inflammation. Trends Biochem Sci 2005, 30(1):43-52.
5. Perkins N.D. Post-translational modifications regulating the activity and function of the nuclear factor kappa B pathway. Oncogene 2006, 25(51):6717-6730.
6. Grivennikov S.I., Karin M. Inflammation and oncogenesis: a vicious connection. Curr Opin Genet Dev 2010, 20(1):65-71.
7. Staudt L.M. Oncogenic activation of NF-kappaB. Cold Spring Harb Perspect Biol 2010, 2(6):a000109.
8. Ruland J. Return to homeostasis: downregulation of NF-kappaB responses. Nat Immunol 2011, 12(8):709-714.
9. Sakurai H., Chiba H., Miyoshi H., Sugita T., Toriumi W. IkappaB kinases phosphorylate NF-kappaB p65 subunit on serine 536 in the transactivation domain. J Biol Chem 1999, 274(43):30353-30356.
10. Nelson D.E., Ihekwaba A.E., Elliott M., Johnson J.R., Gibney C.A., Foreman B.E., et al. Oscillations in NF-kappaB signaling control the dynamics of gene expression. Science 2004, 306(5696):704-708.
11. Neumann M., Naumann M. Beyond IkappaBs: alternative regulation of NF-kappaB activity. FASEB J 2007, 21(11):2642-2654.
12. Chen L.F., Greene W.C. Regulation of distinct biological activities of the NF-kappaB transcription factor complex by acetylation. J Mol Med 2003, 81(9):549-557.
13. Perkins N.D. Regulation of NF-kappaB by atypical activators and tumour suppressors. Biochem Soc Trans 2004, 32(Pt 6):936-939.
14. Rocha S., Campbell K., Perkins N.D. p53-and Mdm2-independent repression of NF-κB transactiviation by the ARF tumor suppressor. Mol Cell 2003, 12:15-25.
15. Geng H., Wittwer T., Dittrich-Breiholz O., Kracht M., Schmitz M.L. Phosphorylation of NF-kappaB p65 at Ser468 controls its COMMD1-dependent ubiquitination and target gene-specific proteasomal elimination. EMBO Rep 2009, 10(4):381-386.
16. Sakurai H., Suzuki S., Kawasaki N., Nakano H., Okazaki T., Chino A., et al. Tumor necrosis factor-alpha-induced IKK phosphorylation of NF-kappaB p65 on serine 536 is mediated through the TRAF2, TRAF5, and TAK1 signaling pathway. J Biol Chem 2003, 278(38):36916-36923.
17. Bohuslav J., Chen L.F., Kwon H., Mu Y., Greene W.C. p53 induces NF-kappaB activation by an IkappaB kinase-independent mechanism involving phosphorylation of p65 by ribosomal S6 kinase 1. J Biol Chem 2004, 279(25):26115-26125.
18. Sasaki C.Y., Barberi T.J., Ghosh P., Longo D.L. Phosphorylation of RelA/p65 on serine 536 defines an I{kappa}B{alpha}-independent NF-{kappa}B pathway. J Biol Chem 2005, 280(41):34538-34547.
19. Zhong H., Voll R.E., Ghosh S. Phosphorylation of NF-kappa B p65 by PKA stimulates transcriptional activity by promoting a novel bivalent interaction with the coactivator CBP/p300. Mol Cell 1998, 1(5):661-671.
20. Zhong H., May M.J., Jimi E., Ghosh S. The phosphorylation status of nuclear NF-kappa B determines its association with CBP/p300 or HDAC-1. Mol Cell 2002, 9(3):625-636.
21. Liu Y., Mayo M.W., Nagji A.S., Smith P.W., Ramsey C.S., Li D., et al. Phosphorylation of RelA/p65 promotes DNMT-1 recruitment to chromatin and represses transcription of the tumor metastasis suppressor gene BRMS1. Oncogene 2012, 31(9):1143-1154.
22. Chen L.F., Williams S.A., Mu Y., Nakano H., Duerr J.M., Buckbinder L., et al. NF-kappaB RelA phosphorylation regulates RelA acetylation. Mol Cell Biol 2005, 25(18):7966-7975.
23. Wang J., An H., Mayo M.W., Baldwin A.S., Yarbrough W.G. LZAP, a putative tumor suppressor, selectively inhibits NF-kappaB. Cancer Cell 2007, 12(3):239-251.
24. Lu G., Wang Y. Functional diversity of mammalian type 2C protein phosphatase isoforms: new tales from an old family. Clin Exp Pharmacol Physiol 2008, 35(2):107-112.
25. Lu X., An H., Jin R., Zou M., Guo Y., Su P.F., et al. PPM1A is a RelA phosphatase with tumor suppressor-like activity. Oncogene 2014, 33(22):2918-2927.
26. Yang J., Fan G.H., Wadzinski B.E., Sakurai H., Richmond A. Protein phosphatase 2A interacts with and directly dephosphorylates RelA. J Biol Chem 2001, 276(51):47828-47833.
27. Li S., Wang L., Berman M.A., Zhang Y., Dorf M.E. RNAi screen in mouse astrocytes identifies phosphatases that regulate NF-kappaB signaling. Mol Cell 2006, 24(4):497-509.
28. Barford D., Das A.K., Egloff M.P. The structure and mechanism of protein phosphatases: insights into catalysis and regulation. Annu Rev Biophys Biomol Struct 1998, 27:133-164.
29. Moorhead G.B., Trinkle-Mulcahy L., Ulke-Lemee A. Emerging roles of nuclear protein phosphatases. Nat Rev Mol Cell Biol 2007, 8(3):234-244.
30. Barford D. Molecular mechanisms of the protein serine/threonine phosphatases. Trends Biochem Sci 1996, 21(11):407-412.
31. Fiscella M., Zhang H., Fan S., Sakaguchi K., Shen S., Mercer W.E., et al. Wip1, a novel human protein phosphatase that is induced in response to ionizing radiation in a p53-dependent manner. Proc Natl Acad Sci U S A 1997, 94(12):6048-6053.
32. Lu X., Nguyen T.A., Moon S.H., Darlington Y., Sommer M., Donehower L.A. The type 2C phosphatase Wip1: an oncogenic regulator of tumor suppressor and DNA damage response pathways. Cancer Metastasis Rev 2008, 27(2):123-135.
33. Chew J., Biswas S., Shreeram S., Humaidi M., Wong E.T., Dhillion M.K., et al. WIP1 phosphatase is a negative regulator of NF-kappaB signalling. Nat Cell Biol 2009, 11(5):659-666.
34. Lowe J.M., Cha H., Yang Q., Fornace A.J. Nuclear factor-kappaB (NF-kappaB) is a novel positive transcriptional regulator of the oncogenic Wip1 phosphatase. J Biol Chem 2010, 285(8):5249-5257.
35. Mann D.J., Campbell D.G., McGowan C.H., Cohen P.T. Mammalian protein serine/threonine phosphatase 2C: cDNA cloning and comparative analysis of amino acid sequences. Biochim Biophys Acta 1992, 1130(1):100-104.
36. Das A.K., Helps N.R., Cohen P.T., Barford D. Crystal structure of the protein serine/threonine phosphatase 2C at 2.0Å resolution. EMBO J 1996, 15(24):6798-6809.
37. Lifschitz-Mercer B., Sheinin Y., Ben-Meir D., Bramante-Schreiber L., Leider-Trejo L., Karby S., et al. Protein phosphatase 2Calpha expression in normal human tissues: an immunohistochemical study. Histochem Cell Biol 2001, 116(1):31-39.
38. Lin X., Duan X., Liang Y.Y., Su Y., Wrighton K.H., Long J., et al. PPM1A functions as a Smad phosphatase to terminate TGFbeta signaling. Cell 2006, 125(5):915-928.
39. Lammers T., Lavi S. Role of type 2C protein phosphatases in growth regulation and in cellular stress signaling. Crit Rev Biochem Mol Biol 2007, 42(6):437-461.
40. Shohat M., Ben-Meir D., Lavi S. Protein phosphatase magnesium dependent 1A (PPM1A) plays a role in the differentiation and survival processes of nerve cells. PLoS ONE 2012, 7(2):e32438.
41. Sun W., Yu Y., Dotti G., Shen T., Tan X., Savoldo B., et al. PPM1A and PPM1B act as IKKbeta phosphatases to terminate TNFalpha-induced IKKbeta-NF-kappaB activation. Cell Signal 2009, 21(1):95-102.
42. Kim J.S., Rho B., Lee T.H., Lee J.M., Kim S.J., Park J.H. The interaction of hepatitis B virus X protein and protein phosphatase type 2 Calpha and its effect on IL-6. Biochem Biophys Res Commun 2006, 351(1):253-258.
43. Ching Y.P., Qi Z., Wang J.H. Cloning of three novel neuronal Cdk5 activator binding proteins. Gene 2000, 242(1/2):285-294.
44. Wang J., He X., Luo Y., Yarbrough W.G. A novel ARF-binding protein (LZAP) alters ARF regulation of HDM2. Biochem J 2006, 393(Pt 2):489-501.
45. Jiang H., Wu J., He C., Yang W., Li H. Tumor suppressor protein C53 antagonizes checkpoint kinases to promote cyclin-dependent kinase 1 activation. Cell Res 2009, 19(4):458-468.
46. An H., Lu X., Liu D., Yarbrough W.G. LZAP inhibits p38 MAPK (p38) phosphorylation and activity by facilitating p38 association with the wild-type p53 induced phosphatase 1 (WIP1). PLoS ONE 2011, 6(1):e16427.
47. Jiang H., Luo S., Li H. Cdk5 activator-binding protein C53 regulates apoptosis induced by genotoxic stress via modulating the G2/M DNA damage checkpoint. J Biol Chem 2005, 280(21):20651-20659.
48. Kwon J., Cho H.J., Han S.H., No J.G., Kwon J.Y., Kim H. A novel LZAP-binding protein, NLBP, inhibits cell invasion. J Biol Chem 2010, 285(16):12232-12240.
49. Plevin M.J., Mills M.M., Ikura M. The LxxLL motif: a multifunctional binding sequence in transcriptional regulation. Trends Biochem Sci 2005, 30(2):66-69.
50. Pike A.C., Brzozowski A.M., Hubbard R.E. A structural biologist's view of the oestrogen receptor. J Steroid Biochem Mol Biol 2000, 74(5):261-268.
51. Orlowski R.Z., Baldwin J., Albert S. NF-[kappa]B as a therapeutic target in cancer. Trends Mol Med 2002, 8(8):385-389.
52. Rayet B., Gelinas C. Aberrant rel/nfκb genes and activity in human cancer. Oncogene 1999, 18:6938-6947.
53. Baldwin A.S. Control of oncogenesis and cancer therapy resistance by the transcription factor NF-{{kappa}}B. J Clin Invest 2001, 107(3):241-246.
54. Thu Y.M., Richmond A. NF-kappaB inducing kinase: a key regulator in the immune system and in cancer. Cytokine Growth Factor Rev 2010, 21(4):213-226.
55. Madonna G., Ullman C.D., Gentilcore G., Palmieri G., Ascierto P.A. NF-kappaB as potential target in the treatment of melanoma. J Transl Med 2012, 10:53. [review].
56. Arun P., Brown M.S., Ehsanian R., Chen Z., Van Waes C. Nuclear NF-kappaB p65 phosphorylation at serine 276 by protein kinase A contributes to the malignant phenotype of head and neck cancer. Clin Cancer Res 2009, 15(19):5974-5984.
57. Dong G., Loukinova E., Chen Z., Gangi L., Chanturita T.I., Liu E.T., et al. Molecular profiling of transformed and metastatic murine squamous carcinoma cells by differential display and cDNA microarray reveals altered expression of multiple genes related to growth, apoptosis angiogenesis, and the NF-{{kappa}}B signal pathway. Cancer Res 2001, 61(12):4797-4808.
58. Duffey D.C., Chen Z., Dong G., Ondrey F.G., Wolf J.S., Brown K., et al. Expression of a dominant-negative mutant inhibitor-{{kappa}}B{{alpha}} of nuclear factor-{{kappa}}B in human head and neck squamous cell carcinoma inhibits survival, proinflammatory cytokine expression, and tumor growth in vivo. Cancer Res 1999, 59(14):3468-3474.
59. Jemal A., Siegel R., Ward E., Murray T., Xu J., Thun M.J. Cancer statistics. CA Cancer J Clin 2007, 57(1):43-66.
60. Nelson W.G., De Marzo A.M., Isaacs W.B. Prostate cancer. N Engl J Med 2003, 349(4):366-381.
61. Min J., Zaslavsky A., Fedele G., McLaughlin S.K., Reczek E.E., De Raedt T., et al. An oncogene-tumor suppressor cascade drives metastatic prostate cancer by coordinately activating Ras and nuclear factor-kappaB. Nat Med 2010, 16(3):286-294.
62. Setlur S.R., Royce T.E., Sboner A., Mosquera J.M., Demichelis F., Hofer M.D., et al. Integrative microarray analysis of pathways dysregulated in metastatic prostate cancer. Cancer Res 2007, 67(21):10296-10303.
63. Mumby M. PP2A: unveiling a reluctant tumor suppressor. Cell 2007, 130(1):21-24.
64. Schonthal A.H. Role of serine/threonine protein phosphatase 2A in cancer. Cancer Lett 2001, 170(1):1-13.
65. Yang J., Richmond A. Constitutive IkappaB kinase activity correlates with nuclear factor-kappaB activation in human melanoma cells. Cancer Res 2001, 61(12):4901-4909.
66. Calin G.A., di Iasio M.G., Caprini E., Vorechovsky I., Natali P.G., Sozzi G., et al. Low frequency of alterations of the alpha (PPP2R1A) and beta (PPP2R1B) isoforms of the subunit A of the serine-threonine phosphatase 2A in human neoplasms. Oncogene 2000, 19(9):1191-1195.
67. Guo Y., Xu F., Lu T., Duan Z., Zhang Z. Interleukin-6 signaling pathway in targeted therapy for cancer. Cancer Treat Rev 2012, 38(7):904-910.
68. Yao J.S., Zhai W., Young W.L., Yang G.Y. Interleukin-6 triggers human cerebral endothelial cells proliferation and migration: the role for KDR and MMP-9. Biochem Biophys Res Commun 2006, 342(4):1396-1404.
69. Zhang J., Patel L., Pienta K.J. Targeting chemokine (C-C motif) ligand 2 (CCL2) as an example of translation of cancer molecular biology to the clinic. Prog Mol Biol Transl Sci 2010, 95:31-53.
70. Ohta M., Kitadai Y., Tanaka S., Yoshihara M., Yasui W., Mukaida N., et al. Monocyte chemoattractant protein-1 expression correlates with macrophage infiltration and tumor vascularity in human gastric carcinomas. Int J Oncol 2003, 22(4):773-778.
71. Azevedo A., Cunha V., Teixeira A.L., Medeiros R. IL-6/IL-6R as a potential key signaling pathway in prostate cancer development. World J Clin Oncol 2011, 2(12):384-396.
72. Wolf M.J., Hoos A., Bauer J., Boettcher S., Knust M., Weber A., et al. Endothelial CCR2 signaling induced by colon carcinoma cells enables extravasation via the JAK2-Stat5 and p38MAPK pathway. Cancer Cell 2012, 22(1):91-105.
73. Mueller L., Seggern L.V., Schumacher J., Goumas F., Wilms C., Braun F., et al. TNF-alpha similarly induces IL-6 and MCP-1 in fibroblasts from colorectal liver metastases and normal liver fibroblasts. Biochem Biophys Res Commun 2010, 397(3):586-591.
74. Qian B.Z., Li J., Zhang H., Kitamura T., Zhang J., Campion L.R., et al. CCL2 recruits inflammatory monocytes to facilitate breast-tumour metastasis. Nature 2011, 475(7355):222-225.
75. Sosnoski D.M., Krishnan V., Kraemer W.J., Dunn-Lewis C., Mastro A.M. Changes in cytokines of the bone microenvironment during breast cancer metastasis. Int J Breast Cancer 2012, 2012:160265.
76. Craig M.J., Loberg R.D. CCL2 (monocyte chemoattractant protein-1) in cancer bone metastases. Cancer Metastasis Rev 2006, 25(4):611-619.
77. Lu Y., Cai Z., Galson D.L., Xiao G., Liu Y., George D.E., et al. Monocyte chemotactic protein-1 (MCP-1) acts as a paracrine and autocrine factor for prostate cancer growth and invasion. Prostate 2006, 66(12):1311-1318.
78. Zhao J.J., Pan K., Li J.J., Chen Y.B., Chen J.G., Lv L., et al. Identification of LZAP as a new candidate tumor suppressor in hepatocellular carcinoma. PLoS ONE 2011, 6(10):e26608.
79. Lu X., Nannenga B., Donehower L.A. PPM1D dephosphorylates Chk1 and p53 and abrogates cell cycle checkpoints. Genes Dev 2005, 19(10):1162-1174.
80. Fujimoto H., Onishi N., Kato N., Takekawa M., Xu X.Z., Kosugi A., et al. Regulation of the antioncogenic Chk2 kinase by the oncogenic Wip1 phosphatase. Cell Death Differ 2006, 13(7):1170-1180.
81. Oliva-Trastoy M., Berthonaud V., Chevalier A., Ducrot C., Marsolier-Kergoat M.C., Mann C., et al. The Wip1 phosphatase (PPM1D) antagonizes activation of the Chk2 tumour suppressor kinase. Oncogene 2007, 26(10):1449-1458.
82. Yamaguchi H., Durell S.R., Chatterjee D.K., Anderson C.W., Appella E. The Wip1 phosphatase PPM1D dephosphorylates SQ/TQ motifs in checkpoint substrates phosphorylated by PI3K-like kinases. Biochemistry 2007, 46(44):12594-12603.
83. Bulavin D.V., Phillips C., Nannenga B., Timofeev O., Donehower L.A., Anderson C.W., et al. Inactivation of the Wip1 phosphatase inhibits mammary tumorigenesis through p38 MAPK-mediated activation of the p16(Ink4a)-p19(Arf) pathway. Nat Genet 2004, 36(4):343-350.
84. Dong J., Jimi E., Zhong H., Hayden M.S., Ghosh S. Repression of gene expression by unphosphorylated NF-kappaB p65 through epigenetic mechanisms. Genes Dev 2008, 22(9):1159-1173.