HSC70 coordinates COP9 signalosome and SCF ubiquitin ligase activity to enable a prompt stress response

Nishimura, Shunsuke; Kioka, Hidetaka; Ding, Shan; Hakui, Hideyuki; Shinomiya, Haruki; Tanabe, Kazuya; Hitsumoto, Tatsuro; Matsuoka, Ken; Kato, Hisakazu; Tsukamoto, Osamu; Asano, Yoshihiro; Takashima, Seiji; Enchev, Radoslav I.; Sakata, Yasushi

doi:https://doi.org/10.1038/s44319-025-00376-x

HSC70 coordinates COP9 signalosome and SCF ubiquitin ligase activity to enable a prompt stress response

Nishimura, Shunsuke; Kioka, Hidetaka; Ding, Shan et al.

EMBO Reports, 2025, 26(5), 1344-1366

Number of Access:9（2025-04-30 13:18 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/101052

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Title	HSC70 coordinates COP9 signalosome and SCF ubiquitin ligase activity to enable a prompt stress response
Creator	CreatorName Nishimura, Shunsuke
	NRID 1000070642099 1000070642099 researchmap permalink hkioka hkioka Scopus Author ID 36872909700 36872909700 CreatorName Kioka, Hidetaka
	CreatorName Ding, Shan
	CreatorName Hakui, Hideyuki
	NRID 1000010908213 1000010908213 researchmap permalink h.shinomiya h.shinomiya CreatorName Shinomiya, Haruki
	CreatorName Tanabe, Kazuya
	CreatorName Hitsumoto, Tatsuro
	NRID 1000090826190 1000090826190 researchmap permalink k-matsuoka k-matsuoka Scopus Author ID 56168659200 56168659200 CreatorName Matsuoka, Ken
	NRID 1000030589312 1000030589312 ORCID 0000-0003-4619-3680 0000-0003-4619-3680 researchmap permalink kato-hisa-1979 kato-hisa-1979 Scopus Author ID 55476241300 55476241300 CreatorName Kato, Hisakazu
	NRID 1000080589151 1000080589151 ORCID 0000-0002-9504-8001 0000-0002-9504-8001 researchmap permalink o_tsukamoto o_tsukamoto Scopus Author ID 7006371707 7006371707 CreatorName Tsukamoto, Osamu
	NRID 1000060527670 1000060527670 researchmap permalink osaka-med-yasano osaka-med-yasano Scopus Author ID 7401729290 7401729290 CreatorName Asano, Yoshihiro
	NRID 1000090379272 1000090379272 researchmap permalink read0118567 read0118567 Scopus Author ID 7402272558 7402272558 CreatorName Takashima, Seiji
	CreatorName Enchev, Radoslav I.
	NRID 1000000397671 1000000397671 ORCID 0000-0002-5618-4721 0000-0002-5618-4721 researchmap permalink C4589 C4589 Scopus Author ID 35395964700 35395964700 CreatorName Sakata, Yasushi
Subject	COP9 Signalosome
	HSC70
	Proteostasis
	SCF Ubiquitin Ligase
	Stress Response
Description	Nishimura S., Kioka H., Ding S., et al. HSC70 coordinates COP9 signalosome and SCF ubiquitin ligase activity to enable a prompt stress response. EMBO Reports 26, 1344 (2025); https://doi.org/10.1038/s44319-025-00376-x.
Abstract	The SCF (SKP1/CUL1/F-box protein) ubiquitin ligase complex plays a protective role against external stress, such as ultraviolet irradiation. The emergence of substrates activates SCF through neddylation, the covalent attachment of ubiquitin-like protein NEDD8 to CUL1. After substrate degradation, SCF is inactivated through deneddylation by COP9-signalosome (CSN), a solo enzyme that can deneddylate SCF. How the activity of CSN and SCF is coordinated within the cell is not fully understood. Here, we find that heat-shock cognate 70 (HSC70) chaperone coordinates SCF and CSN activation dependent on the neddylation status and substrate availability. Under basal conditions and low substrate availability, HCS70 directly enhances CSN deneddylation activity, thereby reducing SCF activity. Under SCF-activated conditions, HSC70 interacts with neddylated SCF and enhances its ubiquitination activity. The alternative interaction between HSC70 and CSN or neddylated SCF is regulated by the presence or absence of SCF substrates. The knockdown of HSC70 decreases SCF-mediated substrate ubiquitination, resulting in vulnerability against ultraviolet irradiation. Our work demonstrates the pivotal role of HSC70 in the alternative activation of CSN deneddylation and SCF substrate ubiquitination, which enables a prompt stress response.
Publisher	Springer Science and Business Media Deutschland GmbH
Source Title	EMBO Reports
Volume (Issue)	26(5)
Page	1344-1366
Date of Issued	2025-03-10
Language	English
Handle URL	https://hdl.handle.net/11094/101052
PISSN	1469221X
eISSN	14693178
Relation.isIdenticalTo	DOI (Publisher Version) https://doi.org/10.1038/s44319-025-00376-x
Access Rights	open access
CopyRight	This article is licensed under a Creative Commons Attribution 4.0 International License.
oaire:version	Version of Record
Category	学術雑誌論文 Journal Article

Resource Type	journal article
Local Type	Journal Article
DCTERMS.bibliographicCitation	EMBO Reports. 2025, 26(5), p. 1344-1366
DC.title	HSC70 coordinates COP9 signalosome and SCF ubiquitin ligase activity to enable a prompt stress response
DC.creator	Nishimura, Shunsuke
	Kioka, Hidetaka
	Ding, Shan
	Hakui, Hideyuki
	Shinomiya, Haruki
	Tanabe, Kazuya
	Hitsumoto, Tatsuro
	Matsuoka, Ken
	Kato, Hisakazu
	Tsukamoto, Osamu
	Asano, Yoshihiro
	Takashima, Seiji
	Enchev, Radoslav I.
	Sakata, Yasushi
DC.publisher	Springer Science and Business Media Deutschland GmbH
DC.language' scheme='DCTERMS.RFC1766	English
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2025-03-10
DC.identifier	https://doi.org/10.1038/s44319-025-00376-x
DC.subject	COP9 Signalosome
	HSC70
	Proteostasis
	SCF Ubiquitin Ligase
	Stress Response
DC.description	Nishimura S., Kioka H., Ding S., et al. HSC70 coordinates COP9 signalosome and SCF ubiquitin ligase activity to enable a prompt stress response. EMBO Reports 26, 1344 (2025); https://doi.org/10.1038/s44319-025-00376-x.
DCTERMS.abstract	The SCF (SKP1/CUL1/F-box protein) ubiquitin ligase complex plays a protective role against external stress, such as ultraviolet irradiation. The emergence of substrates activates SCF through neddylation, the covalent attachment of ubiquitin-like protein NEDD8 to CUL1. After substrate degradation, SCF is inactivated through deneddylation by COP9-signalosome (CSN), a solo enzyme that can deneddylate SCF. How the activity of CSN and SCF is coordinated within the cell is not fully understood. Here, we find that heat-shock cognate 70 (HSC70) chaperone coordinates SCF and CSN activation dependent on the neddylation status and substrate availability. Under basal conditions and low substrate availability, HCS70 directly enhances CSN deneddylation activity, thereby reducing SCF activity. Under SCF-activated conditions, HSC70 interacts with neddylated SCF and enhances its ubiquitination activity. The alternative interaction between HSC70 and CSN or neddylated SCF is regulated by the presence or absence of SCF substrates. The knockdown of HSC70 decreases SCF-mediated substrate ubiquitination, resulting in vulnerability against ultraviolet irradiation. Our work demonstrates the pivotal role of HSC70 in the alternative activation of CSN deneddylation and SCF substrate ubiquitination, which enables a prompt stress response.
DC.rights	This article is licensed under a Creative Commons Attribution 4.0 International License.
DC.format	101052
citation_title	HSC70 coordinates COP9 signalosome and SCF ubiquitin ligase activity to enable a prompt stress response
citation_author	Nishimura, Shunsuke
	Kioka, Hidetaka
	Ding, Shan
	Hakui, Hideyuki
	Shinomiya, Haruki
	Tanabe, Kazuya
	Hitsumoto, Tatsuro
	Matsuoka, Ken
	Kato, Hisakazu
	Tsukamoto, Osamu
	Asano, Yoshihiro
	Takashima, Seiji
	Enchev, Radoslav I.
	Sakata, Yasushi
citation_publisher	Springer Science and Business Media Deutschland GmbH
citation_language	English
citation_date	2025-03-10
citation_journal_title	EMBO Reports
citation_volume	26
citation_issue	5
citation_firstpage	1344
citation_lastpage	1366
citation_doi	https://doi.org/10.1038/s44319-025-00376-x
citation_public_url	https://hdl.handle.net/11094/101052

HSC70 coordinates COP9 signalosome and SCF ubiquitin ligase activity to enable a prompt stress response

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