title: Negative regulation of RelA phosphorylation: emerging players and their roles in cancer.
abstract: NF-κB signaling contributes to human disease processes, notably inflammatory diseases and cancer. Many advances have been made in understanding mechanisms responsible for abnormal NF-κB activation with RelA post-translational modification, particularly phosphorylation, proven to be critical for RelA function. While the majority of studies have focused on identifying kinases responsible for NF-κB phosphorylation and pathway activation, recently progress has also been made in understanding the negative regulators important for restraining RelA activity. Here we summarize negative regulators of RelA phosphorylation, their targeting sites in RelA and biological functions through negative regulation of RelA activation. Finally, we emphasize the tumor suppressor-like roles that these negative regulators can assume in human cancers.
authors.affiliation: Department of Cancer Biology, Vanderbilt University, Nashville, TN, USA; Department of Medicine, University of California at San Francisco, San Francisco, CA, USA.
authors.forename: Xinyuan
authors.initials: X
authors.lastname: Lu
authors.affiliation: Division of Otolaryngology, Department of Surgery, Yale University, New Haven, CT, USA; Department of Pathology, Yale University, New Haven, CT, USA; Yale Cancer Center, New Haven, CT, USA. Electronic address: christine.purcell@yale.edu.
authors.forename: Wendell G
authors.initials: WG
authors.lastname: Yarbrough
mesh_terms: D018797:Cell Cycle Proteins; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D015398:Signal Transduction; D051996:Transcription Factor RelA / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins
chemical_list: C405928:CDK5RAP3 protein, human; D018797:Cell Cycle Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; C498143:RELA protein, human; D051996:Transcription Factor RelA; D025521:Tumor Suppressor Proteins; D010744:Phosphoric Monoester Hydrolases
keywords: LZAP; NF-κB; PPM1A; Phosphatase; Tumor suppressor