Differential effects of SUMO1 and SUMO2 on circadian protein PER2 stability and function

Abstract Posttranslational modification (PTM) of core circadian clock proteins, including Period2 (PER2), is required for proper circadian regulation. PER2 function is regulated by casein kinase 1 (CK1)-mediated phosphorylation and ubiquitination but little is known about other PER2 PTMs or their in...

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Autores principales:	Ling-Chih Chen, Yung-Lin Hsieh, Grace Y. T. Tan, Tai-Yun Kuo, Yu-Chi Chou, Pang-Hung Hsu, Wendy W. Hwang-Verslues
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c8703bfb39e34a1f8846b341bee43c82
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spelling	oai:doaj.org-article:c8703bfb39e34a1f8846b341bee43c822021-12-02T15:33:13ZDifferential effects of SUMO1 and SUMO2 on circadian protein PER2 stability and function10.1038/s41598-021-93933-y2045-2322https://doaj.org/article/c8703bfb39e34a1f8846b341bee43c822021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-93933-yhttps://doaj.org/toc/2045-2322Abstract Posttranslational modification (PTM) of core circadian clock proteins, including Period2 (PER2), is required for proper circadian regulation. PER2 function is regulated by casein kinase 1 (CK1)-mediated phosphorylation and ubiquitination but little is known about other PER2 PTMs or their interaction with PER2 phosphorylation. We found that PER2 can be SUMOylated by both SUMO1 and SUMO2; however, SUMO1 versus SUMO2 conjugation had different effects on PER2 turnover and transcriptional suppressor function. SUMO2 conjugation facilitated PER2 interaction with β-TrCP leading to PER2 proteasomal degradation. In contrast, SUMO1 conjugation, mediated by E3 SUMO-protein ligase RanBP2, enhanced CK1-mediated PER2S662 phosphorylation, inhibited PER2 degradation and increased PER2 transcriptional suppressor function. PER2 K736 was critical for both SUMO1- and SUMO2-conjugation. A PER2K736R mutation was sufficient to alter PER2 protein oscillation and reduce PER2-mediated transcriptional suppression. Together, our data revealed that SUMO1 versus SUMO2 conjugation acts as a determinant of PER2 stability and function and thereby affects the circadian regulatory system and the expression of clock-controlled genes.Ling-Chih ChenYung-Lin HsiehGrace Y. T. TanTai-Yun KuoYu-Chi ChouPang-Hung HsuWendy W. Hwang-VersluesNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ling-Chih Chen Yung-Lin Hsieh Grace Y. T. Tan Tai-Yun Kuo Yu-Chi Chou Pang-Hung Hsu Wendy W. Hwang-Verslues Differential effects of SUMO1 and SUMO2 on circadian protein PER2 stability and function
description	Abstract Posttranslational modification (PTM) of core circadian clock proteins, including Period2 (PER2), is required for proper circadian regulation. PER2 function is regulated by casein kinase 1 (CK1)-mediated phosphorylation and ubiquitination but little is known about other PER2 PTMs or their interaction with PER2 phosphorylation. We found that PER2 can be SUMOylated by both SUMO1 and SUMO2; however, SUMO1 versus SUMO2 conjugation had different effects on PER2 turnover and transcriptional suppressor function. SUMO2 conjugation facilitated PER2 interaction with β-TrCP leading to PER2 proteasomal degradation. In contrast, SUMO1 conjugation, mediated by E3 SUMO-protein ligase RanBP2, enhanced CK1-mediated PER2S662 phosphorylation, inhibited PER2 degradation and increased PER2 transcriptional suppressor function. PER2 K736 was critical for both SUMO1- and SUMO2-conjugation. A PER2K736R mutation was sufficient to alter PER2 protein oscillation and reduce PER2-mediated transcriptional suppression. Together, our data revealed that SUMO1 versus SUMO2 conjugation acts as a determinant of PER2 stability and function and thereby affects the circadian regulatory system and the expression of clock-controlled genes.
format	article
author	Ling-Chih Chen Yung-Lin Hsieh Grace Y. T. Tan Tai-Yun Kuo Yu-Chi Chou Pang-Hung Hsu Wendy W. Hwang-Verslues
author_facet	Ling-Chih Chen Yung-Lin Hsieh Grace Y. T. Tan Tai-Yun Kuo Yu-Chi Chou Pang-Hung Hsu Wendy W. Hwang-Verslues
author_sort	Ling-Chih Chen
title	Differential effects of SUMO1 and SUMO2 on circadian protein PER2 stability and function
title_short	Differential effects of SUMO1 and SUMO2 on circadian protein PER2 stability and function
title_full	Differential effects of SUMO1 and SUMO2 on circadian protein PER2 stability and function
title_fullStr	Differential effects of SUMO1 and SUMO2 on circadian protein PER2 stability and function
title_full_unstemmed	Differential effects of SUMO1 and SUMO2 on circadian protein PER2 stability and function
title_sort	differential effects of sumo1 and sumo2 on circadian protein per2 stability and function
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/c8703bfb39e34a1f8846b341bee43c82
work_keys_str_mv	AT lingchihchen differentialeffectsofsumo1andsumo2oncircadianproteinper2stabilityandfunction AT yunglinhsieh differentialeffectsofsumo1andsumo2oncircadianproteinper2stabilityandfunction AT graceyttan differentialeffectsofsumo1andsumo2oncircadianproteinper2stabilityandfunction AT taiyunkuo differentialeffectsofsumo1andsumo2oncircadianproteinper2stabilityandfunction AT yuchichou differentialeffectsofsumo1andsumo2oncircadianproteinper2stabilityandfunction AT panghunghsu differentialeffectsofsumo1andsumo2oncircadianproteinper2stabilityandfunction AT wendywhwangverslues differentialeffectsofsumo1andsumo2oncircadianproteinper2stabilityandfunction
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Differential effects of SUMO1 and SUMO2 on circadian protein PER2 stability and function

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