Cited by 163Ubiquitin and proteasome pathwaysMicrotubule and mitosis dynamicsCancer-related Molecular Pathways

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

Yamashita, Yukiko M., Nakaseko, Yukinobu, Samejima, Itaru, Kumada, Kazuki, Yamada, Hiroshi, Michaelson, David, Yanagida, Mitsuhiro·1996·Nature

DOI 10.1038/384276a0

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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 Sti1 (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.

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Authors: Yamashita, Y. M., Nakaseko, Y., Samejima, I., Kumada, K., Yamada, H., Michaelson, D., & Yanagida, M.
Affiliations: Kyoto University (JP)
ORCID: Yamashita, Yukiko M.
Samejima, Itaru
Kumada, Kazuki
Yamada, Hiroshi
Yanagida, Mitsuhiro
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 1996-11
Volume: 384
Issue: 6606
Pages: 276-279
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/384276a0
OpenAlex: W1990634825
Cited by: 163
References: 26
Citations by year: 2026: 2 · 2025: 1 · 2024: 4 · 2022: 2 · 2020: 1 · 2019: 1 · 2018: 4 · 2016: 4 · 2014: 5 · 2013: 6 · 2012: 3
FWCI: 8.66
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
Keywords: anaphase-promoting complex, cAMP/PKA signaling, protein kinase A regulatory subunit, cAMP phosphodiesterase, STI1, sister chromatid separation, anaphase onset, heavy metal stress, Schizosaccharomyces pombe, ubiquitin ligase
MeSH terms: Cyclic AMP, Anaphase, Cloning, Molecular, Genes, Fungal, Ligases, Mutation, Schizosaccharomyces, Cyclins, Cyclic AMP-Dependent Protein Kinases, Metals, Heavy

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

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