Distinct functions of steroidogenic factor-1 (NR5A1) in the nucleus and the centrosome

Abstract

Steroidogenic Factor 1 (SF-1, Ad4bp, NR5A1) is a nuclear receptor expressed mainly in the adrenals and gonads. It activates the transcription of genes in steroidogenesis, reproduction, and energy metabolism. In addition, it also regulates the growth and differentiation of adrenogonadal primodial cells. SF-1 resides in the nucleus and the centrosome. SF-1 moves dynamically in the nucleus, and SF-1 location and activity are dynamically regulated by post-translational modifications. In the centrosome, SF-1 maintains genomic integrity by controlling centrosome homeostasis. SF-1 prevents centrosome amplification by restricting aberrant activation of centrosomal DNA-PK. Upon SF-1 removal, DNA-PK is activated and centrosomes are amplified. This leads to genomic instability and cell growth defects. These data indicate that SF-1 at both the nucleus and the centrosome contributes to cell growth control, but the mechanisms of SF-1 action in different locations are different.