title: TC-1 is a novel tumorigenic and natively disordered protein associated with thyroid cancer.
abstract: A novel gene, thyroid cancer 1 (TC-1), was found recently to be overexpressed in thyroid cancer. TC-1 shows no homology to any of the known thyroid cancer-associated genes. We have produced stable transformants of normal thyroid cells that express the TC-1 gene, and these cells show increased proliferation rates and anchorage-independent growth in soft agar. Apoptosis rates also are decreased in the transformed cells. We also have expressed recombinant TC-1 protein and have undertaken a structural and functional characterization of the protein. The protein is monomeric and predominantly unstructured under conditions of physiologic salt and pH. This places it in the category of natively disordered proteins, a rapidly expanding group of proteins, many members of which play critical roles in cell regulation processes. We show that the protein can be phosphorylated by cyclic AMP-dependent protein kinase and protein kinase C, and the activity of both of these kinases is up-regulated when cells are stably transfected with TC-1. These results suggest that overexpression of TC-1 may be important in thyroid carcinogenesis.
authors.affiliation: School of Molecular and Microbial Biosciences and Discipline of Medicine, University of Sydney, Australia.
authors.forename: Margaret
authors.initials: M
authors.lastname: Sunde
authors.forename: Kristine C Y
authors.initials: KC
authors.lastname: McGrath
authors.forename: Lei
authors.initials: L
authors.lastname: Young
authors.forename: Jacqueline M
authors.initials: JM
authors.lastname: Matthews
authors.forename: Elizabeth L
authors.initials: EL
authors.lastname: Chua
authors.forename: Joel P
authors.initials: JP
authors.lastname: Mackay
authors.forename: Alison K
authors.initials: AK
authors.lastname: Death
mesh_terms: D017209:Apoptosis / Q000502:physiology; D002448:Cell Adhesion / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D045744:Cell Line, Tumor; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D006801:Humans; D009363:Neoplasm Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D019906:Nuclear Magnetic Resonance, Biomolecular; D010766:Phosphorylation; D011487:Protein Conformation; D011493:Protein Kinase C / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D013964:Thyroid Neoplasms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D014162:Transfection
chemical_list: D009363:Neoplasm Proteins; C418741:TCIM protein, human; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C