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Hsp90 enhances degradation of oxidized calmodulin by the 20 S proteasome

Jennifer E Whittier1, Yijia Xiong, Martin C Rechsteiner

  • 1Cell Biology and Biochemistry Group, Biological Sciences Division, Pacific Northwest National Laboratory, Richland, Washington 99352, USA.

The Journal of Biological Chemistry
|August 21, 2004
PubMed

Insights

The molecular chaperone Hsp90 is essential for the 20 S proteasome to degrade oxidized calmodulin (CaM(ox)). Hsp90 selectively binds CaM(ox), promoting its proteasomal degradation.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cellular Stress Response

Background:

  • The 20 S proteasome degrades abnormal proteins, especially during oxidative stress.
  • The molecular chaperone Hsp90 is often found associated with the 20 S proteasome.

Purpose of the Study:

  • To investigate the role of Hsp90 in the proteasomal degradation of oxidized calmodulin (CaM(ox)).

Main Methods:

  • Purification of 20 S proteasomes devoid of Hsp90.
  • Assessing CaM(ox) degradation in the presence and absence of Hsp90.
  • Utilizing proteasome and Hsp90 inhibitors.
  • Measuring protein binding interactions.

Main Results:

  • Purified 20 S proteasome alone does not degrade CaM(ox); Hsp90 is required.
  • CaM(ox) degradation is inhibited by specific proteasome and Hsp90 inhibitors and enhanced by ATP.
  • Unoxidized calmodulin is not significantly degraded.
  • Hsp90 selectively binds to CaM(ox), not unoxidized calmodulin.

Conclusions:

  • Hsp90 is crucial for the 20 S proteasome to degrade oxidized and partially unfolded calmodulin.
  • Hsp90 acts as a selective targeting factor for damaged proteins to the proteasome.

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