title: Transglutaminase 2 and NF-κB: an odd couple that shapes breast cancer phenotype.
abstract: Owing to numerous pro-survival target genes, aberrant activation of the NF-κB transcription factor is associated with a drug-resistant phenotype and aggressive breast tumor behavior. Transglutaminase 2 (TG2), a ubiquitously expressed protein cross-linking enzyme, activates NF-κB through a non-conventional mechanism that disables the IκBα inhibitor. Our group has recently documented that the TG2 gene (termed TGM2) is a direct transcriptional target of NF-κB. These developments uncover a novel self-reinforcing molecular feedback loop where TG2 activates NF-κB and, in turn, NF-κB directly upregulates the transcription of TGM2. This manuscript reviews the literature that supports the existence of the TG2/NF-κB signaling loop, the nature of the signal transduction that activates this loop, and the phenotypic consequences stemming from the aberrant activation of this novel signaling mechanism in breast cancer.
authors.affiliation: Department of Biochemistry and Molecular Biology, UF-Shands Cancer Center, College of Medicine, University of Florida, 1600 SW Archer Road, P.O. Box 1000245, Gainesville, FL 32610, USA. kdbrown1@ufl.edu
authors.forename: Kevin D
authors.initials: KD
authors.lastname: Brown
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D019008:Drug Resistance, Neoplasm; D005260:Female; D019204:GTP-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D015398:Signal Transduction / Q000235:genetics; D011503:Transglutaminases / Q000235:genetics* / Q000378:metabolism*
chemical_list: D016328:NF-kappa B; C000717608:TGM2 protein, human; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins