Steroidogenic Factor 1 (NR5A1) resides in centrosomes and maintains genomic stability by controlling centrosome homeostasis

Lai, Pao-Yen; Wang, Chung‐Yu; Chen, Wei Yi; Kao, Yung-Hsin; Tsai, Hsiao-Lun; Tachibana, Taro; Chang, Wenli; Chung, Bon Chu

doi:10.1038/cdd.2011.54

Cited by 28 publications

(29 citation statements)

References 34 publications

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“…1a,b). Consistent with previous reports [18][19][20][21] , the treated cells were decreased in number, probably due to decreased proliferation (Fig. 1c,d).…”

Section: Resultssupporting

confidence: 81%

Glycolytic genes are targets of the nuclear receptor Ad4BP/SF-1

et al. 2014

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Genetic deficiencies in transcription factors can lead to the loss of certain types of cells and tissue. The steroidogenic tissue-specific nuclear receptor Ad4BP/SF-1 (NR5A1) is one such gene, because mice in which this gene is disrupted fail to develop the adrenal gland and gonads. However, the specific role of Ad4BP/SF-1 in these biological events remains unclear. Here we use chromatin immunoprecipitation sequencing to show that nearly all genes in the glycolytic pathway are regulated by Ad4BP/SF-1. Suppression of Ad4BP/SF-1 by small interfering RNA reduces production of the energy carriers ATP and nicotinamide adenine dinucleotide phosphate, as well as lowers expression of genes involved in glucose metabolism. Together, these observations may explain tissue dysgenesis as a result of Ad4BP/SF-1 gene disruption in vivo. Considering the function of estrogen-related receptor a, the present study raises the possibility that certain types of nuclear receptors regulate sets of genes involved in metabolic pathways to generate energy carriers.

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“…1a,b). Consistent with previous reports [18][19][20][21] , the treated cells were decreased in number, probably due to decreased proliferation (Fig. 1c,d).…”

Section: Resultssupporting

confidence: 81%

Glycolytic genes are targets of the nuclear receptor Ad4BP/SF-1

et al. 2014

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“…We have previously found that SF-1 resides in both the nucleus and centrosomes (5). Here, we found that SF-1 was present at the centriole at all cell cycle stages, including the interphase and mitosis (see Fig.…”

Section: Resultssupporting

confidence: 49%

“…Although the functions of SF-1 in transcription have been well characterized, the mechanism by which SF-1 participates in cell growth control remains largely unknown. Our earlier results show that SF-1 resides in the centrosome and controls centrosomal homeostasis (5). Here, we show that centrosomal SF-1 prevents centrosome overduplication by restricting the activities of DNA-PK/Akt signaling within the centrosome; this can be one of the means by which SF-1 controls the growth and survival of adrenocortical progenitor cells.…”

Section: Discussionmentioning

confidence: 92%

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Steroidogenic Factor 1 (NR5A1) Maintains Centrosome Homeostasis in Steroidogenic Cells by Restricting Centrosomal DNA-Dependent Protein Kinase Activation

Wang

Kao

Lai

et al. 2013

Molecular and Cellular Biology

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bSteroidogenic factor 1 (SF-1 or NR5A1) is a nuclear receptor that controls adrenogenital cell growth and differentiation. Adrenogenital primordial cells from SF-1 knockout mice die of apoptosis, but the mechanism by which SF-1 regulates cell survival is not entirely clear. Besides functioning in the nucleus, SF-1 also resides in the centrosome and controls centrosome homeostasis. Here, we show that SF-1 restricts centrosome overduplication by inhibiting aberrant activation of DNA-dependent protein kinase (DNA-PK) in the centrosome. SF-1 was found to be associated with Ku70/Ku80 only in the centrosome, sequestering them from the catalytic subunit of DNA-PK (DNA-PKcs). In the absence of SF-1, DNA-PKcs was recruited to the centrosome and activated, causing aberrant activation of centrosomal Akt and cyclin-dependent kinase 2 (CDK2)/cyclin A and leading to centrosome overduplication. Centrosome overduplication caused by SF-1 depletion was averted by the elimination of DNA-PKcs, Ku70/80, or cyclin A or by the inhibition of CDK2 or Akt. In the nucleus, SF-1 did not interact with Ku70/80, and SF-1 depletion did not activate a nuclear DNA damage response. Centriole biogenesis was also unaffected. Thus, centrosomal DNA-PK signaling triggers centrosome overduplication, and this centrosomal event, but not the nuclear DNA damage response, is controlled by SF-1.

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“…This soluble pool of VDAC3b fractionates distinctly from mitochondria in sucrose gradients and, instead, co-fractionates with the high-density peak of γ-tubulin, which corresponds to the position of centrosomes. 43 VDAC3b is also found in a subcellular fraction that is depleted of mitochondria but contains the centrosomal proteins γ-tubulin and Mps1. Thus, we hypothesize that centrosomal VDAC3 adopts a conformation where its strongly suggest that a centrosomal pool of VDAC3 modulates centriole assembly by recruiting Mps1 to the centrosome.…”

Section: Discussionmentioning

confidence: 99%