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Updated: Jun 2, 2026

Pull-down of Calmodulin-binding Proteins
07:51

Pull-down of Calmodulin-binding Proteins

Published on: January 23, 2012

Calmodulin protects androgen receptor from calpain-mediated breakdown in prostate cancer cells

Arun Sivanandam1, Shalini Murthy, Kannagi Chinnakannu

  • 1Vattikuti Urology Institute, Henry Ford Hospital, Detroit, Michigan 48202, USA.

Journal of Cellular Physiology
|April 21, 2011
PubMed

Insights

Targeting androgen receptor (AR) protein breakdown is key for prostate cancer cure. Calmodulin (CaM) inactivation sensitizes AR to calpain (Cpn) breakdown, offering a potential new treatment strategy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Androgen receptor (AR) targeted therapies are standard for prostate cancer but not curative.
  • Castration-resistant prostate cancer (CRPC) cells maintain AR activity, necessitating AR protein elimination strategies.

Purpose of the Study:

  • To investigate the role of calmodulin (CaM) and calpain (Cpn) in the degradation of AR in prostate cancer cells.
  • To explore the potential of combined CaM inactivation and Cpn activation for AR protein elimination.

Main Methods:

  • Prostate cancer cells were treated with anti-CaM drugs and calcimycin (a Cpn activator).
  • AR protein and mRNA levels were assessed using Western blotting and RT-PCR.
  • Purified recombinant human AR (rhAR) was subjected to proteolysis assays with Cpn and CaM.

Main Results:

  • Combined treatment with anti-CaM drugs and calcimycin significantly reduced AR protein levels without affecting AR mRNA.
  • AR protein turnover increased, indicating degradation rather than transcriptional inhibition.
  • Purified AR was degraded by Cpn, and CaM binding protected AR from this degradation.

Conclusions:

  • Androgen receptor is a calpain target, and bound calmodulin protects it from degradation.
  • Combined anti-CaM drugs and Cpn activators may represent a curative strategy for AR-dependent prostate cancers.

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