The GSK-3β-FBXL21 Axis Contributes to Circadian TCAP Degradation and Skeletal Muscle Function.

Wirianto, M; Yang, J; Kim, E; Gao, S; Paudel, KR; Choi, JM; Choe, J; Gloston, GF; Ademoji, P; Parakramaweera, R; Jin, J; Esser, KA; Jung, SY; Geng, Y-J; Lee, HK; Chen, Z; Yoo, S-H

The GSK-3β-FBXL21 Axis Contributes to Circadian TCAP Degradation and Skeletal Muscle Function.

Wirianto, M Yang, J Kim, E Gao, S Paudel, KR Choi, JM Choe, J Gloston, GF Ademoji, P Parakramaweera, R Jin, J Esser, KA Jung, SY Geng, Y-J Lee, HK Chen, Z Yoo, S-H

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Publisher:: CELL PRESS
Publication Type:: Journal Article
Citation:: Cell reports, 2020, 32, (11)
Issue Date:: 2020-09

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Field	Value	Language
dc.contributor.author	Wirianto, M
dc.contributor.author	Yang, J
dc.contributor.author	Kim, E
dc.contributor.author	Gao, S
dc.contributor.author	Paudel, KR
dc.contributor.author	Choi, JM
dc.contributor.author	Choe, J
dc.contributor.author	Gloston, GF
dc.contributor.author	Ademoji, P
dc.contributor.author	Parakramaweera, R
dc.contributor.author	Jin, J
dc.contributor.author	Esser, KA
dc.contributor.author	Jung, SY
dc.contributor.author	Geng, Y-J
dc.contributor.author	Lee, HK
dc.contributor.author	Chen, Z
dc.contributor.author	Yoo, S-H
dc.date.accessioned	2020-10-27T05:56:36Z
dc.date.available	2020-08-21
dc.date.available	2020-10-27T05:56:36Z
dc.date.issued	2020-09
dc.identifier.citation	Cell reports, 2020, 32, (11)
dc.identifier.issn	2211-1247
dc.identifier.issn	2211-1247
dc.identifier.uri	http://hdl.handle.net/10453/143540
dc.description.abstract	FBXL21 is a clock-controlled E3 ligase modulating circadian periodicity via subcellular-specific CRYPTOCHROME degradation. How FBXL21 regulates tissue-specific circadian physiology and what mechanism operates upstream is poorly understood. Here we report the sarcomere component TCAP as a cytoplasmic substrate of FBXL21. FBXL21 interacts with TCAP in a circadian manner antiphasic to TCAP accumulation in skeletal muscle, and circadian TCAP oscillation is disrupted in Psttm mice with an Fbxl21 hypomorph mutation. GSK-3β phosphorylates FBXL21 and TCAP to activate FBXL21-mediated, phosphodegron-dependent TCAP degradation. GSK-3β inhibition or knockdown diminishes FBXL21-Cul1 complex formation and delays FBXL21-mediated TCAP degradation. Finally, Psttm mice show significant skeletal muscle defects, including impaired fiber size, exercise tolerance, grip strength, and response to glucocorticoid-induced atrophy, in conjunction with cardiac dysfunction. These data highlight a circadian regulatory pathway where a GSK-3β-FBXL21 functional axis controls TCAP degradation via SCF complex formation and regulates skeletal muscle function.
dc.format	Print
dc.language	eng
dc.publisher	CELL PRESS
dc.relation.ispartof	Cell reports
dc.relation.isbasedon	10.1016/j.celrep.2020.108140
dc.rights	info:eu-repo/semantics/openAccess
dc.subject	0601 Biochemistry and Cell Biology, 1116 Medical Physiology
dc.title	The GSK-3β-FBXL21 Axis Contributes to Circadian TCAP Degradation and Skeletal Muscle Function.
dc.type	Journal Article
utslib.citation.volume	32
utslib.location.activity	United States
utslib.for	0601 Biochemistry and Cell Biology
utslib.for	1116 Medical Physiology
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney
utslib.copyright.status	open_access	*
pubs.consider-herdc	false
dc.date.updated	2020-10-27T05:56:27Z
pubs.issue	11
pubs.publication-status	Published
pubs.volume	32
utslib.citation.issue	11

Abstract:

FBXL21 is a clock-controlled E3 ligase modulating circadian periodicity via subcellular-specific CRYPTOCHROME degradation. How FBXL21 regulates tissue-specific circadian physiology and what mechanism operates upstream is poorly understood. Here we report the sarcomere component TCAP as a cytoplasmic substrate of FBXL21. FBXL21 interacts with TCAP in a circadian manner antiphasic to TCAP accumulation in skeletal muscle, and circadian TCAP oscillation is disrupted in Psttm mice with an Fbxl21 hypomorph mutation. GSK-3β phosphorylates FBXL21 and TCAP to activate FBXL21-mediated, phosphodegron-dependent TCAP degradation. GSK-3β inhibition or knockdown diminishes FBXL21-Cul1 complex formation and delays FBXL21-mediated TCAP degradation. Finally, Psttm mice show significant skeletal muscle defects, including impaired fiber size, exercise tolerance, grip strength, and response to glucocorticoid-induced atrophy, in conjunction with cardiac dysfunction. These data highlight a circadian regulatory pathway where a GSK-3β-FBXL21 functional axis controls TCAP degradation via SCF complex formation and regulates skeletal muscle function.

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http://hdl.handle.net/10453/143540