Marty W. Mayo

Education

  • PhD, East Carolina University, Greenville, NC
  • Postdoc, University of North Carolina, Chapel Hill, NC
  • BS, Clemson University, Clemson, SC

Primary Appointment

  • Associate Professor, Biochemistry and Molecular Genetics

Contact

Research Interest(s)

Transcriptional Regulation by NFKB

Research Description

Within cells there exists a fine balance between survival and death. One of the earliest steps in the development of cancer is the ability of a cell to escape death. It is now well established that cells die through an orderly process known as programmed cell death or apoptosis. However, cells are able to overcome apoptotic pathways by upregulating gene products that inactivate the cell death machinery.

Our group was among the first to describe that the transcription factor NF-kB is involved in the inhibition of cell death. Classical NF-kB, composed of a p50/p65 neterodimer protein complex, is ubiquitously expressed in cells. The activation of NF-kB by various stimuli, including tumor necrosis factor, stimulates the production of gene products that protect cells from apoptosis. Interestingly, the involvement of NF-kB in suppressing cell death implicates this transcription factor in cancer progression. Moreover, we have found that NF-kB is activated in response to chemotherapy and irradiation, and is required to overcome cell death by these agents. Therefore, the use of NF-kB inhibitors would have important implications for increasing the effectiveness of standard cancer therapy.

Our laboratory is broadly interested in understanding transcrptional control of NF-kB by addressing four basic questions. First, we would like to determine the signaling pathways that are utilized by stress inducers to activate NF-kB-dependent gene expression. Second, we would like to elucidate how these stress pathways induce the transcriptional activation of NF-kB. In particular, determine whether DNA-binding, chromatin rearrangement and recruitment of co-activators are important in this process. Third, we would like to identify gene products regulated by NF-kB that are responsible for blocking apoptosis. Finally, we would like to identify and characterize pharmacological agents that inhibit NF-kB activation and determine whether these agents can be used in combination with standard cancer therapies. To address these questions our laboratory utilizes human cancer cell lines, as well as more complex human xenograft tumor models propagated in nude mice. It is a combination of these two experimental models that wil allow us to understand NF-kB regulated processes and to determine how these components are important in human cancer.

Selected Publications

  • Allison D, Wamsley J, Kumar M, Li D, Gray L, Hart G, Jones D, Mayo M. Modification of RelA by O-linked N-acetylglucosamine links glucose metabolism to NF-κB acetylation and transcription. Proceedings of the National Academy of Sciences of the United States of America. 2012. PMID: 23027940
  • Locke L, Mayo M, Yoo A, Williams M, Berr S. PET imaging of tumor associated macrophages using mannose coated 64Cu liposomes. Biomaterials. 2012;33(31): 7785-93. PMID: 22840225
  • Glidden E, Gray L, Vemuru S, Li D, Harris T, Mayo M. Multiple site acetylation of Rictor stimulates mammalian target of rapamycin complex 2 (mTORC2)-dependent phosphorylation of Akt protein. The Journal of biological chemistry. 2011;287(1): 581-8. PMID: 22084251 | PMCID: PMC3249112
  • Liu Y, Mayo M, Nagji A, Smith P, Ramsey C, Li D, Jones D. Phosphorylation of RelA/p65 promotes DNMT-1 recruitment to chromatin and represses transcription of the tumor metastasis suppressor gene BRMS1. Oncogene. 2011;31(9): 1143-54. PMID: 21765477 | PMCID: PMC3219802
  • Allison D, Mayo M. StIKKing together: do multiple IKK pathways cooperate in the DNA-damage response? Molecular cell. 2010;37(4): 453-4. PMID: 20188663
  • Mikesh L, Kumar M, Erdag G, Hogan K, Molhoek K, Mayo M, Slingluff C. Evaluation of molecular markers of mesenchymal phenotype in melanoma. Melanoma research. 2010;20(6): 485-95. PMID: 20856146 | PMCID: PMC3229868
  • Sturgill T, Stoddard P, Cohn S, Mayo M. The promoter for intestinal cell kinase is head-to-head with F-Box 9 and contains functional sites for TCF7L2 and FOXA factors. Molecular cancer. 2010;9 104. PMID: 20459822 | PMCID: PMC2876993
  • Xu X, Hoang S, Mayo M, Bekiranov S. Application of machine learning methods to histone methylation ChIP-Seq data reveals H4R3me2 globally represses gene expression. BMC bioinformatics. 2010;11 396. PMID: 20653935 | PMCID: PMC2928206
  • Ramsey C, Yeung F, Stoddard P, Li D, Creutz C, Mayo M. Copine-I represses NF-kappaB transcription by endoproteolysis of p65. Oncogene. 2008;27(25): 3516-26. PMID: 18212740
  • Hoberg J, Popko A, Ramsey C, Mayo M. IkappaB kinase alpha-mediated derepression of SMRT potentiates acetylation of RelA/p65 by p300. Molecular and cellular biology. 2005;26(2): 457-71. PMID: 16382138 | PMCID: PMC1346914
  • Cinar B, Yeung F, Konaka H, Mayo M, Freeman M, Zhau H, Chung L. Identification of a negative regulatory cis-element in the enhancer core region of the prostate-specific antigen promoter: implications for intersection of androgen receptor and nuclear factor-kappaB signalling in prostate cancer cells. The Biochemical journal. 2004;379 421-31. PMID: 14715080 | PMCID: PMC1224078
  • Hoberg J, Yeung F, Mayo M. SMRT derepression by the IkappaB kinase alpha: a prerequisite to NF-kappaB transcription and survival. Molecular cell. 2004;16(2): 245-55. PMID: 15494311
  • Yeung F, Hoberg J, Ramsey C, Keller M, Jones D, Frye R, Mayo M. Modulation of NF-kappaB-dependent transcription and cell survival by the SIRT1 deacetylase. The EMBO journal. 2004;23(12): 2369-80. PMID: 15152190 | PMCID: PMC423286
  • Mayo M, Denlinger C, Broad R, Yeung F, Reilly E, Shi Y, Jones D. Ineffectiveness of histone deacetylase inhibitors to induce apoptosis involves the transcriptional activation of NF-kappa B through the Akt pathway. The Journal of biological chemistry. 2003;278(21): 18980-9. PMID: 12649266