20S cyclosome complex formation and proteolytic activity inhibited by the cAMP/PKA pathway

Y. M. Yamashita, Y. Nakaseko, I. Samejima, K. Kumada, H. Yamada, D. Michaelson, M. Yanagida

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137 Citations (Scopus)

Abstract

THE 20S cyclosome complex (also known as the anaphase-promoting complex) has ubiquitin ligase activity and is required for mitotic cyclin destruction and sister chromatid separation. The formation and activation of the 20S cyclosome complex is regulated by an unknown mechanism. Here we show that Cut4 (ref. 6) is an essential component of the cyclosome in fission yeast. Cut4 shares sequence similarity with BimE, a protein that regulates mitosis in Aspergillus nidulans. Mutations in cut4 result in hypersensitivity to cyclic AMP and to stress-inducing heavy metals, inhibition of the onset of anaphase, disruption of the 20S complex, and inhibition of mitotic cyclin ubiquitination. These phenotypes are fully suppressed by cAMP phosphodiesterase and the protein kinase A (PKA) regulatory subunit and weakly suppressed by Stil (an activator of the Hsp70 and Hsp90 chaperones). Suppression correlates with the amount of 20S complex, indicating that cyclosome formation and activation is inhibited by the cAMP/PKA pathway.

Original languageEnglish
Pages (from-to)276-279
Number of pages4
JournalNature
Volume384
Issue number6606
DOIs
Publication statusPublished - 1996
Externally publishedYes

ASJC Scopus subject areas

  • General

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