title: Rab1b overexpression modifies Golgi size and gene expression in HeLa cells and modulates the thyrotrophin response in thyroid cells in culture.
abstract: Rab1b belongs to the Rab-GTPase family that regulates membrane trafficking and signal transduction systems able to control diverse cellular activities, including gene expression. Rab1b is essential for endoplasmic reticulum-Golgi transport. Although it is ubiquitously expressed, its mRNA levels vary among different tissues. This work aims to characterize the role of the high Rab1b levels detected in some secretory tissues. We report that, in HeLa cells, an increase in Rab1b levels induces changes in Golgi size and gene expression. Significantly, analyses applied to selected genes, KDELR3, GM130 (involved in membrane transport), and the proto-oncogene JUN, indicate that the Rab1b increase acts as a molecular switch to control the expression of these genes at the transcriptional level, resulting in changes at the protein level. These Rab1b-dependent changes require the activity of p38 mitogen-activated protein kinase and the cAMP-responsive element-binding protein consensus binding site in those target promoter regions. Moreover, our results reveal that, in a secretory thyroid cell line (FRTL5), Rab1b expression increases in response to thyroid-stimulating hormone (TSH). Additionally, changes in Rab1b expression in FRTL5 cells modify the specific TSH response. Our results show, for the first time, that changes in Rab1b levels modulate gene transcription and strongly suggest that a Rab1b increase is required to elicit a secretory response.
authors: Centro de Investigaciones en Bioquímica Clínica e Inmunología, Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba 5000, Argentina.
authors: Nahuel
authors: N
authors: Romero
authors: Catherine I
authors: CI
authors: Dumur
authors: Hernán
authors: H
authors: Martinez
authors: Iris A
authors: IA
authors: García
authors: Pablo
authors: P
authors: Monetta
authors: Ileana
authors: I
authors: Slavin
authors: Luciana
authors: L
authors: Sampieri
authors: Nicolas
authors: N
authors: Koritschoner
authors: Alexander A
authors: AA
authors: Mironov
authors: Maria Antonietta
authors: MA
authors: De Matteis
authors: Cecilia
authors: C
authors: Alvarez
mesh_terms: D001692:Biological Transport; D004721:Endoplasmic Reticulum / Q000378:metabolism / Q000648:ultrastructure; D005786:Gene Expression Regulation / Q000187:drug effects; D006056:Golgi Apparatus / Q000378:metabolism* / Q000648:ultrastructure; D006367:HeLa Cells; D006801:Humans; D000090063:Proto-Oncogene Mas; D015398:Signal Transduction; D013961:Thyroid Gland / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D013972:Thyrotropin / Q000378:metabolism / Q000494:pharmacology; D014158:Transcription, Genetic; D020761:rab1 GTP-Binding Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D013972:Thyrotropin; C529587:Rab1B protein, human; D020761:rab1 GTP-Binding Proteins