Filamin-A fragment localizes to the nucleus to regulate androgen receptor and coactivator functions.

The androgen receptor (AR), a nuclear transcription factor, mediates male sexual differentiation, and its excessive action is associated with prostate cancer. We have characterized a negative regulatory domain in the AR hinge region, which interacted with filamin A (FLNa), an actin-binding cytoskeletal protein. FLNa interfered with AR interdomain interactions and ...
competed with the coactivator transcriptional intermediary factor 2 to specifically down-regulate AR function. Although full-length FLNa was predominantly cytoplasmic, a C-terminal 100-kDa fragment of FLNa colocalized with AR to the nucleus. This naturally occurring FLNa fragment repressed AR transactivation and disrupted AR interdomain interactions and transcriptional intermediary factor 2-activated AR function in a manner reminiscent of full-length FLNa, raising the possibility that the inhibitory effects of cytoplasmic FLNa may be transduced through this fragment, which can localize to the nucleus and form part of the pre-initiation complex. This unanticipated role of FLNa adds to the growing evidence for the involvement of cytoskeletal proteins in transcription regulation.
Mesh Terms:
Amino Acid Sequence, Binding Sites, Cell Line, Cell Nucleus, Contractile Proteins, Hela Cells, Humans, Male, Microfilament Proteins, Models, Biological, Molecular Sequence Data, Mutation, Nuclear Receptor Coactivator 2, Peptide Fragments, Prostatic Neoplasms, Protein Structure, Tertiary, Receptors, Androgen, Recombinant Proteins, Transcription Factors, Transcriptional Activation, Two-Hybrid System Techniques
Proc. Natl. Acad. Sci. U.S.A.
Date: Apr. 15, 2003
Download Curated Data For This Publication
8471
Switch View:
  • Interactions 2