Ku Is a Novel Transcriptional Recycling Coactivator of the Androgen Receptor in Prostate Cancer Cells

Abstract

The androgen receptor (AR) dynamically assembles and disassembles multicomponent receptor complexes in order to respond rapidly and reversibly to fluctuations in androgen levels. We are interested in identifying the basal factors that compose the AR aporeceptor and holoreceptor complexes and impact the transcriptional process. Using tandem mass spectroscopy analysis, we identified the trimeric DNA-dependent protein kinase (

Site-specific Androgen Receptor Serine Phosphorylation Linked to Epidermal Growth Factor-dependent Growth of Castration-recurrent Prostate Cancer

“…Ku-70/80 subunits were also implicated in AR transcriptional recycling (33). To address the 5 g, lane 3).…”

ATM Inhibition Potentiates Death of Androgen Receptor-inactivated Prostate Cancer Cells with Telomere Dysfunction

“…These observations raise an intriguing possibility that AR may play a role in telomere DNA replication or repair and that aberrant telomeres in AR-inactivated prostate cancer cells may result from impaired telomere DNA replication or repair. Consistent with this possibility are the observations that AR co-immunoprecipitates with TRF-1 and TRF-2 (3), AR is associated with telomere DNA (4), and AR is implicated to play a non-transcriptional role in DNA replication (36,45) and possibly in repair of nuclear DNA (46). However, it remains to be determined whether AR inactivation interferes with either replication or repair of telomere DNA.…”

NKX3.1 contributes to S phase entry and regulates DNA damage response (DDR) in prostate cancer cell lines

“…Thus, NKX3.1 overexpression in PC-3 cells results in a distinct response to topo I inhibition, which was similar in LNCaP cells that can be induced with androgens. As it was previously reported that NKX3.1 repressed transcription together with the Groucho complex [11] and regulated the pro-oxidant enzyme expressions by HDAC1 recruitment [13], NKX3.1 may be the major regulator of transcription, cell cycle and repair in prostate cells [16,17,21,22].…”

“…Androgen-responsive LNCaP cells (passage number [10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25] were propagated in RPMI1640 (Invitrogen, UK) medium supplemented with 10% heat-inactivated FBS (Invitrogen, UK). Cells were serum starved in the presence of 2% for 48 h and 0.5% for an additional 24 h in CT-FBS containing RPMI1640.…”

“…TOPORS, a strong E3 ubiquitin ligase, promotes proteasomal degradation of NKX3.1 through direct interaction, predisposing cells to oncogenic transformation by providing an irreversible growth advantage as the first steps in prostate carcinogenesis [14]. Recently, it has been reported that NKX3.1 relocates to the nucleus and enhances the cleavage and re-ligation abilities of the topoisomerase I (topo I) enzyme through direct association [15,16]. ATM and ATR activities are influenced by NKX3.1 expression, which protects cells against IR-and mitomycin C-induced DNA damage [17].…”