The Gsk-3Β-Fbxl21 Axis Regulates Tcap Via Ubiquitin-Mediated Proteasomal Pathway In The Cytoplasm

<p>Protein turnover is one of the most essential mechanisms controlling circadian rhythms. F-Box and Leucine Rich Repeat Protein21 (FBXL21) is a circadian E3 ligase which shows oscillatory mRNA transcripts and protein levels. It was previously found to perform subcellular compartment-specific E3 ligase activities targeting the core clock proteins CRYPTOCHROME(CRY)1/2. Here we identified a new sarcomeric target substrate, Telethonin(TCAP), which also shows circadian oscillation in its mRNA transcript and protein expression and, importantly, interaction with FBXL21 in an anti-phasic manner. Via computational and pharmacological tests, we identified Glycogen Synthase Kinase-3β(GSK-3β) as a regulator of FBXL21. Biochemical and molecular characterizations demonstrated that GSK-3β interacts with both FBXL21 and TCAP and affects Skp, Cullin1(Cul1), F-box containing (SCF) complex/E3 ligase-Substrate complex formation. Interestingly, GSK-3β knockdown significantly inhibited FBXL21-CUL11 and FBXL21-TCAP complex formation. These results revealed a new circadian regulatory pathway that FBXL21 regulates TCAP via ubiquitin-mediated proteasomal pathway in the cytoplasm coordinatively with GSK-3β.</p>

Name thesis:degree_name

Masters of Science (MS)

Level thesis:degree_level

Thesis (MS)

Year dc:date.available

2019

Authors dc:creator

• Yang, Jiah
• <p>0000-0003-2312-8536</p>

Contributors dc:contributor

• Seung-Hee Yoo
• Mark J. Burish
• Zheng Chen

• FBXL21
• TCAP
• Telethonin
• GSK-3β
• E3 ligase
• SCF complex
• Circadian
• Ubiquitin
• Proteasomal pathway
• Biochemistry
• Cell Biology
• Medicine and Health Sciences
• Molecular Biology
• Musculoskeletal, Neural, and Ocular Physiology

Repository record dc:identifier

https://digitalcommons.library.tmc.edu/utgsbs_dissertations/927

OAI identifier oai:identifier

oai:digitalcommons.library.tmc.edu:utgsbs_dissertations-1998