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Newly synthesized kinases have one thing in common with teenagers: they can go astray without supervision. As Mandal et al. reveal on page 319, cells keep the regulatory proteins in line by assigning them a bodyguard. The molecular guardian helps kinases avoid premature destruction.

Researchers already knew that the protective protein, Cdc37, teams with the chaperone Hsp90 to help freshly synthesized kinase chains fold into shape. But evidence indicates that Cdc37 also works independently of Hsp90. To pin down Cdc37's other job, the researchers measured the amounts of 65 kinases in yeast cells that produce a defective version of the Cdc37 protein. Levels of 80% of the kinases were lower than in control cells. However, faulty Cdc37 didn't alter gene expression, and translation appeared to run normally, suggesting that the decline occurred after cells fashioned the kinases.

They found that, in cells with defective Cdc37, newly synthesized kinases broke down swiftly. But the kinases escaped destruction if the researchers first added a drug that stalls the proteasome, the cellular garbage disposal that chops up misshapen proteins. Without protection from Cdc37, newly formed kinases appear to get shunted into the proteasome for recycling. Cdc37 latches onto its targets at their active site during or shortly after translation. The researchers suspect that the protein can somehow sense its charges' shape and prevent them from misfolding, which would trigger their demolition.

Mitch Leslie

mitchleslie{at}comcast.net

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Related Article

Cdc37 has distinct roles in protein kinase quality control that protect nascent chains from degradation and promote posttranslational maturation

Atin K. Mandal, Paul Lee, Jennifer A. Chen, Nadinath Nillegoda, Alana Heller, Susan DiStasio, Handy Oen, Jacob Victor, Devi M. Nair, Jeffrey L. Brodsky, and Avrom J. Caplan
J. Cell Biol. 2007 176: 319-328. [Abstract] [Full Text] [PDF]

This Article PDF (Full Text) Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Leslie, M. Search for Related Content PubMed Articles by Leslie, M. Related Collections Related Article Social Bookmarking                      What's this?