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Differential Effects of SUMO1/2 on Circadian Protein PER2 Stability and Function
Differential Effects of SUMO1/2 on Circadian Protein PER2 Stability and Function
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Differential Effects of SUMO1/2 on Circadian Protein PER2 Stability and Function
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Differential Effects of SUMO1/2 on Circadian Protein PER2 Stability and Function
Differential Effects of SUMO1/2 on Circadian Protein PER2 Stability and Function

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Differential Effects of SUMO1/2 on Circadian Protein PER2 Stability and Function
Differential Effects of SUMO1/2 on Circadian Protein PER2 Stability and Function
Paper

Differential Effects of SUMO1/2 on Circadian Protein PER2 Stability and Function

2019,2020
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Overview
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. We found that PER2 can be SUMOylated by both SUMO1 and SUMO2; however, SUMO1 versus SUMO2 conjugation had different effects on PER2 turnover and subcellular localization. SUMO2 conjugation facilitated PER2 degradation. In contrast, SUMO1 conjugation, mediated by E3 SUMO-protein ligase RanBP2, enhanced CK1-mediated PER2S662 phosphorylation and increased PER2 nuclear accumulation, chromatin association and transcriptional suppressor function. PER2 K736 was critical for both SUMO1- and SUMO2-conjugation. A PER2K736R mutation was sufficient to alter circadian periodicity, decrease PER2 nuclear entry and abolish PER2-mediated transcriptional suppression. Together, our data revealed differential effects of SUMO1 versus SUMO2 conjugation on PER2 function and demonstrated the effect of PER2 SUMOylation on the circadian regulatory system and circadian periodicity. Footnotes * Figure 1, Figure 2 and Supplemental files updated