title: NAG-1/GDF15 accumulates in the nucleus and modulates transcriptional regulation of the Smad pathway.
abstract: Protein dynamics, modifications and trafficking are all processes that can modulate protein activity. Accumulating evidence strongly suggests that many proteins have distinctive roles dependent on cellular location. Nonsteroidal anti-inflammatory drug-activated gene-1 (NAG-1) is a transforming growth factor-β (TGF-β) superfamily protein that has a role in cancer, obesity and inflammation. NAG-1 is synthesized and cleaved into a mature peptide, which is ultimately secreted into the extracellular matrix (ECM). In this study, we have found that full-length NAG-1 is expressed in not only the cytoplasm and ECM, but also in the nucleus. NAG-1 is dynamically moved to the nucleus, exported into cytoplasm and further transported into the ECM. We have also found that nuclear NAG-1 contributes to inhibition of the Smad pathway by interrupting the Smad complex. Overall, our study indicates that NAG-1 is localized in the nucleus and provides new evidence that NAG-1 controls transcriptional regulation in the Smad pathway.
authors.affiliation: Department of Biomedical and Diagnostic Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN, USA.
authors.forename: K-W
authors.initials: KW
authors.lastname: Min
authors.affiliation: Department of Biomedical and Diagnostic Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN, USA.
authors.forename: J L
authors.initials: JL
authors.lastname: Liggett
authors.affiliation: Department of Biomedical and Diagnostic Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN, USA.
authors.forename: G
authors.initials: G
authors.lastname: Silva
authors.affiliation: Facility for Biotechnology Resources, CBER, Food and Drug Administration, Bethesda, MD, USA.
authors.forename: W W
authors.initials: WW
authors.lastname: Wu
authors.affiliation: Facility for Biotechnology Resources, CBER, Food and Drug Administration, Bethesda, MD, USA.
authors.forename: R
authors.initials: R
authors.lastname: Wang
authors.affiliation: Facility for Biotechnology Resources, CBER, Food and Drug Administration, Bethesda, MD, USA.
authors.forename: R-F
authors.initials: RF
authors.lastname: Shen
authors.affiliation: Laboratory of Molecular Carcinogenesis, NIH/NIEHS, Research Triangle Park, NC, USA.
authors.forename: T E
authors.initials: TE
authors.lastname: Eling
authors.affiliation: Department of Biomedical and Diagnostic Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN, USA.
authors.forename: S J
authors.initials: SJ
authors.lastname: Baek
mesh_terms: D017209:Apoptosis / Q000235:genetics; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000235:genetics*; D003593:Cytoplasm / Q000235:genetics; D005109:Extracellular Matrix / Q000235:genetics; D055436:Growth Differentiation Factor 15 / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D011401:Promoter Regions, Genetic; D015398:Signal Transduction; D051785:Smad Proteins / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: C526140:GDF15 protein, human; D055436:Growth Differentiation Factor 15; D051785:Smad Proteins