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.
","abstract_html":"<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>","abstract_has_math":false,"creators":["Yang, Jiah","0000-0003-2312-8536
"],"institution":null,"degree_name":"Masters of Science (MS)","degree_level":"Thesis (MS)","degree_discipline":null,"degree_department":null,"school":null,"contributors":["Seung-Hee Yoo","Mark J. Burish","Zheng Chen"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2019,"date_issued":"2019-08-01T07:00:00Z","date_published":"2019-08-01T07:00:00Z","updated_at":"2026-07-24T05:48:59Z","subjects":["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"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://digitalcommons.library.tmc.edu/utgsbs_dissertations/927","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Seung-Hee Yoo","Mark J. Burish","Zheng Chen"]},{"key":"dc:creator","label":"Author","values":["Yang, Jiah","0000-0003-2312-8536
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"]},{"key":"dc:title","label":"Title","values":["The Gsk-3Β-Fbxl21 Axis Regulates Tcap Via Ubiquitin-Mediated Proteasomal Pathway In The Cytoplasm"]}]}],"canonical_facts":{"dc:contributor":["Seung-Hee Yoo","Mark J. Burish","Zheng Chen"],"dc:creator":["Yang, Jiah","0000-0003-2312-8536
"],"dc:date.available":["2019-12-24T08:00:00Z"],"dc:description.abstract":["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.
"],"dc:identifier":["https://digitalcommons.library.tmc.edu/utgsbs_dissertations/927"],"dc:subject":["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"],"dc:title":["The Gsk-3Β-Fbxl21 Axis Regulates Tcap Via Ubiquitin-Mediated Proteasomal Pathway In The Cytoplasm"],"thesis:degree_level":["Thesis (MS)"],"thesis:degree_name":["Masters of Science (MS)"]},"updated_at":"2026-07-24T05:48:59Z"}