title: TNIP1, a retinoic acid receptor corepressor and A20-binding inhibitor of NF-κB, distributes to both nuclear and cytoplasmic locations.
abstract: An increasingly wide range of functions, from repression of NF-κB signaling to protection from apoptosis, is being recognized for tumor necrosis factor α-induced protein 3-interacting protein 1 (TNIP1). The authors recently demonstrated TNIP1 interaction with and repression of liganded retinoic acid receptors, distinguishing it from the more typical NCoR and SMRT corepressors, which function only in the absence of ligand. To improve their understanding of TNIP1's roles in physiologic and pathologic events, the authors examined its distribution in normal and malignant human tissues and cultured cells. They found cytoplasmic and nuclear TNIP1 in normal skin keratinocytes as it colocalized with retinoic acid receptor α, one of the nuclear receptors it corepresses. Nuclear and cytoplasmic TNIP1 was also found in the malignant keratinocytes of squamous cell carcinomas. Compared to adjacent normal tissues of other organs, TNIP1 staining and distribution varied with increased levels in esophageal cancer and marked decreases in prostate cancer. The varying levels and distribution of TNIP1 in normal and disease state tissues could be expected to affect processes in which TNIP1 is involved, such as NF-κB and nuclear receptor signaling, possibly contributing to the disease course or response to therapies targeting these key players of cell growth and differentiation.
authors.affiliation: Graduate Program in Pharmacology & Toxicology, Department of Pharmaceutical Sciences, University of Connecticut, Storrs, Connecticut 06269-3092, USA.
authors.forename: Igor
authors.initials: I
authors.lastname: Gurevich
authors.forename: Carmen
authors.initials: C
authors.lastname: Zhang
authors.forename: Nidhish
authors.initials: N
authors.lastname: Francis
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Aneskievich
mesh_terms: D002467:Cell Nucleus / Q000378:metabolism*; D002478:Cells, Cultured; D056970:Co-Repressor Proteins / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D000078404:Epidermal Cells; D004817:Epidermis / Q000378:metabolism; D006801:Humans; D007231:Infant, Newborn; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D015603:Keratinocytes / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D009369:Neoplasms / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism*; D009928:Organ Specificity; D011485:Protein Binding; D021381:Protein Transport; D018168:Receptors, Retinoic Acid / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D000072482:Retinoic Acid Receptor alpha; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3
chemical_list: D056970:Co-Repressor Proteins; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D016328:NF-kappa B; D009687:Nuclear Proteins; C000607071:RARA protein, human; D018168:Receptors, Retinoic Acid; D011994:Recombinant Proteins; D000072482:Retinoic Acid Receptor alpha; C117046:TNIP1 protein, human; C076529:TNFAIP3 protein, human; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3