Gi and RGS proteins provide biochemical control of androgen receptor nuclear exclusion

Avi Rimler, Ralf Jockers, Zipora Lupowitz, Nava Zisapel*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

Nuclear localization of androgen receptors (ARs) is essential for their activity. Melatonin induces AR nuclear exclusion via increase in cGMP, calcium, and protein kinase C (PKC) activation, presumably through G-protein(s). The effects of regulators of G-protein signaling (RGS) on AR localization were studied in AR-expressing PC3 cells. Gi-specific RGS10 inhibited melatonin but not cGMP-induced AR nuclear exclusion, independent of androgen. No evidence for Gq activation by melatonin was found. However, Gi/Gq-selective RGS4 inhibited AR nuclear exclusion downstream of PKC activation-an effect that was abrogated by constitutively active Gq. RGS10 and RGS4, but not RGS2, ablated the inhibitory effects of melatonin on AR reporter gene activity. For the first time, these data show regulation by Gi and Gi-specific RGS protein-mediated AR nuclear exclusion, which is potentially important in the treatment of AR-dependent cancers and neurodegenerative disorders. They also reveal a role for a Gq protein downstream of PKC activation in AR nuclear localization.

Original languageEnglish
Pages (from-to)1-12
Number of pages12
JournalJournal of Molecular Neuroscience
Volume31
Issue number1
DOIs
StatePublished - Jan 2007

Funding

FundersFunder number
Université de Paris VII
Association pour la Recherche sur le Cancer5513
Institut national de la santé et de la recherche médicale
Centre National de la Recherche Scientifique

    Keywords

    • Androgen receptor
    • Calcium
    • Melatonin
    • Nuclear localization
    • PKC
    • RGS10
    • RGS2
    • RGS4
    • cGMP

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