Calmodulin-androgen receptor (AR) interaction: calcium-dependent, calpain-mediated breakdown of AR in LNCaP prostate cancer cells.

Calmodulin-androgen receptor (AR) interaction: calcium-dependent, calpain-mediated breakdown of AR in LNCaP prostate cancer cells. Research Abstract Details 

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Calmodulin-androgen receptor (AR) interaction: calcium-dependent, calpain-mediated breakdown of AR in LNCaP prostate cancer cells. Abstract Text:

Ronald P Pelley,Kannagi Chinnakannu,Shalini Murthy,Faith M Strickland,Mani Menon,Q Ping Dou,Evelyn R Barrack,G Prem-Veer Reddy,

Chemotherapy of prostate cancer targets androgen receptor (AR) by androgen ablation or antiandrogens, but unfortunately, it is not curative. Our attack on prostate cancer envisions the proteolytic elimination of AR, which requires a fuller understanding of AR turnover. We showed previously that calmodulin (CaM) binds to AR with important consequences for AR stability and function. To examine the involvement of Ca(2+)/CaM in the proteolytic breakdown of AR, we analyzed LNCaP cell extracts that bind to a CaM affinity column for the presence of low molecular weight forms of AR (intact AR size, approximately 114 kDa). Using an antibody directed against the NH(2)-terminal domain (ATD) of AR on Western blots, we identified approximately 76-kDa, approximately 50-kDa, and 34/31-kDa polypeptides in eluates of CaM affinity columns, suggesting the presence of CaM-binding sites within the 31/34-kDa ATD of AR. Under cell-free conditions in the presence of phenylmethylsulfonyl fluoride, AR underwent Ca(2+)-dependent degradation. AR degradation was inhibited by N-acetyl-leu-leu-norleu, an inhibitor of thiol proteases, suggesting the involvement of calpain. In intact cells, AR breakdown was accelerated by raising intracellular Ca(2+) using calcimycin, and increased AR breakdown was reversed with the cell-permeable Ca(2+) chelator bis-(O-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid tetra-(acetoxymethyl)-ester. In CaM affinity chromatography studies, the Ca(2+)-dependent protease calpain was bound to and eluted from the CaM-agarose column along with AR. Caspase-3, which plays a role in AR turnover under stress conditions, did not bind to the CaM column and was present in the proenzyme form. Similarly, AR immunoprecipitates prepared from whole-cell extracts of exponentially growing LNCaP cells contained both calpain and calpastatin. Nuclear levels of calpain and calpastatin (its endogenous inhibitor) changed in a reciprocal fashion as synchronized LNCaP cells progressed from G(1) to S phase. These reciprocal changes correlated with changes in AR level, which increased in late G(1) phase and decreased as S phase progressed. Taken together, these observations suggest potential involvement of AR-bound CaM in calcium-controlled, calpain-mediated breakdown of AR in prostate cancer cells.

Calmodulin-androgen receptor (AR) interaction: calcium-dependent, calpain-mediated breakdown of AR in LNCaP prostate cancer cells. Publishing Authors By Initials

RP Pelley,K Chinnakannu,S Murthy,FM Strickland,M Menon,QP Dou,ER Barrack,GP Reddy,

For similar environment and public health: environment: meteorological factors: atmosphere: weather: sunlight: ultraviolet rays research abstracts see: environment and public health: environment: meteorological factors: atmosphere: weather: sunlight: ultraviolet rays research

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Calmodulin-androgen receptor (AR) interaction: calcium-dependent, calpain-mediated breakdown of AR in LNCaP prostate cancer cells. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: Cancer research

VOLUME: 66

Page Numbers: 11754-62

Journal Abbreviation: Cancer Res.

ISSN: 0008-5472

DAY: 15

MONTH: Dec

YEAR: 2006

Calmodulin-androgen receptor (AR) interaction: calcium-dependent, calpain-mediated breakdown of AR in LNCaP prostate cancer cells. Information

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LANGUAGE: eng

NlmUniqueID: 2984705

Calmodulin-androgen receptor (AR) interaction: calcium-dependent, calpain-mediated breakdown of AR in LNCaP prostate cancer cells. Keywords Mesh Terms:

KEYWORDS: Ultraviolet Rays

MESH TERMS: radiation effects

Chemical & Substance for Abstract: Calmodulin-androgen receptor (AR) interaction: calcium-dependent, calpain-mediated breakdown of AR in LNCaP prostate cancer cells. Information

Substance Name: Calpain

Registry Number: EC 3.4.22.-

Grant and Affiliation Information for Calmodulin-androgen receptor (AR) interaction: calcium-dependent, calpain-mediated breakdown of AR in LNCaP prostate cancer cells.

AFFILIATION: Vattikuti Urology Institute and Department of Dermatology, Henry Ford Hospital, Detroit, MI 48202, USA.

Country: United States

AGENCY: United States NIDDK

GRANT: R01-DK57864

ACRONYM: DK

MEDLINETA: Cancer Res

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