title: Steroidogenic Factor 1 (NR5A1) resides in centrosomes and maintains genomic stability by controlling centrosome homeostasis.
abstract: SF-1 (Steroidogenic Factor 1, NR5A1) is a tissue-specific transcription factor critical for the growth, development and differentiation of steroidogenic and a few other endocrine tissues. But how SF-1 regulates cell growth is not entirely clear. Here we found that SF-1 was localized to the centrosome in addition to the nucleus, and SF-1 depletion by shRNA caused centrosome over-duplication, aberrant mitosis and genomic instability, leading to a reduction of cell number. Centrosome amplification defect was rescued by both wild-type SF-1 and transcription-defective SF-1-G35E, suggesting a non-genomic activity of SF-1 involved in centrosome homeostasis. In addition, we identified in SF-1 a centrosome localization signal, whose overexpression led to reduced localization of both SF-1 and γ-tubulin to the centrosome. Our results uncover a novel role of SF-1 in the control of centrosome homeostasis and genomic stability.
authors.affiliation: Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan.
authors.forename: P-Y
authors.initials: PY
authors.lastname: Lai
authors.forename: C-Y
authors.initials: CY
authors.lastname: Wang
authors.forename: W-Y
authors.initials: WY
authors.lastname: Chen
authors.forename: Y-H
authors.initials: YH
authors.lastname: Kao
authors.forename: H-M
authors.initials: HM
authors.lastname: Tsai
authors.forename: T
authors.initials: T
authors.lastname: Tachibana
authors.forename: W-C
authors.initials: WC
authors.lastname: Chang
authors.forename: B-c
authors.initials: BC
authors.lastname: Chung
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D053145:Cell Nucleus Size; D049109:Cell Proliferation; D002502:Centrioles / Q000378:metabolism*; D042822:Genomic Instability; D006706:Homeostasis; D051379:Mice; D008938:Mitosis; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D021382:Protein Sorting Signals; D021381:Protein Transport; D054339:Steroidogenic Factor 1 / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D021382:Protein Sorting Signals; D054339:Steroidogenic Factor 1; C515058:steroidogenic factor 1, mouse