title: RGS14 is a centrosomal and nuclear cytoplasmic shuttling protein that traffics to promyelocytic leukemia nuclear bodies following heat shock.
abstract: RGS14, a member of the regulator of G-protein signaling (RGS) protein family, possesses an N-terminal RGS domain, two Raf-like Ras-binding domains, and a GoLoco motif, which has GDP dissociation inhibitor activity. In this study we show that unique among the known mammalian RGS proteins, RGS14 localizes in centrosomes. Its first Ras-binding domain is sufficient to target RGS14 to centrosomes. RGS14 also shuttles between the cytoplasm and nucleus, and its nuclear export depends on the CRM-1 nuclear export receptor. Mutation of a nuclear export signal or treatment with leptomycin B causes nuclear accumulation of RGS14 and its association with promyelocytic leukemia protein nuclear bodies. Furthermore, a point mutant defective in nuclear export fails to target to centrosomes, suggesting that nuclear cytoplasmic shuttling is necessary for its proper localization. Mild heat stress, but not proteotoxic or transcription-linked stresses, re-localizes the RGS14 from the cytoplasm to promyelocytic leukemia nuclear bodies. Expression of RGS14, but not point mutants that disrupt the functional activity of its RGS domain or GoLoco motif, enhances the reporter gene activity. The multifunctional domains and the dynamic subcellular localization of RGS14 implicate it in a diverse set of cellular processes including centrosome and nuclear functions and stress-induced signaling pathways.
authors.affiliation: B-cell Molecular Immunology Section, Laboratory of Immunoregulation, NIAID, National Institutes of Health, Bethesda, Maryland 20892-1876, USA.
authors.forename: Hyeseon
authors.initials: H
authors.lastname: Cho
authors.forename: Dong-Uk
authors.initials: DU
authors.lastname: Kim
authors.forename: John H
authors.initials: JH
authors.lastname: Kehrl
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D018385:Centrosome / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D006367:HeLa Cells; D006358:Hot Temperature; D006801:Humans; D045586:Intranuclear Inclusion Bodies / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D041681:NIH 3T3 Cells; D009363:Neoplasm Proteins / Q000378:metabolism*; D015530:Nuclear Matrix / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism*; D000071156:Promyelocytic Leukemia Protein; D021381:Protein Transport; D020710:RGS Proteins / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D025521:Tumor Suppressor Proteins
chemical_list: D009363:Neoplasm Proteins; D009687:Nuclear Proteins; C513293:Pml protein, mouse; D000071156:Promyelocytic Leukemia Protein; D020710:RGS Proteins; C491399:Rgs14 protein, mouse; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C070576:PML protein, human