ArticleCytoskeleton (Hoboken, N.J.)2013
Nonmyofilament-associated troponin T3 nuclear and nucleolar localization sequence and leucine zipper domain mediate muscle cell apoptosis.
Article in Cytoskeleton (Hoboken, N.J.), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 20 citations in OpenAlex.
- Troponin: biology, molecular mechanisms, and multidimensional clinical applications.Molecular biomedicine · 2026Review
- Review
- Non-Canonical Localization of Cardiac Troponins: Expanding Functions or Causing Pathologies?International journal of molecular sciences · 2024Review
- Intranuclear cardiac troponin I plays a functional role in regulatingGenes & diseases · 2022Article
- Cardiac troponin T and autoimmunity in skeletal muscle aging.GeroScience · 2022Article
- The distal arthrogryposis-linked p.R63C variant promotes the stability and nuclear accumulation of TNNT3.Journal of clinical laboratory analysis · 2021Article
- Troponin T3 associates with DNA consensus sequence that overlaps with p53 binding motifs.Experimental gerontology · 2018Article
- Skeletal muscle performance and ageing.Journal of cachexia, sarcopenia and muscle · 2018Review
- Troponin through the looking-glass: emerging roles beyond regulation of striated muscle contraction.Oncotarget · 2018Review
- Will you still need me (CaAging cell · 2017Article
- Calpain inhibition rescues troponin T3 fragmentation, increases Cav1.1, and enhances skeletal muscle force in aging sedentary mice.Aging cell · 2016Article
- Troponin T3 regulates nuclear localization of the calcium channel Cavβ1a subunit in skeletal muscle.Experimental cell research · 2015Article
- Type-1 pericytes accumulate after tissue injury and produce collagen in an organ-dependent manner.Stem cell research & therapy · 2014Article
- Type-2 pericytes participate in normal and tumoral angiogenesis.American journal of physiology. Cell physiology · 2014Article
- Type-1 pericytes participate in fibrous tissue deposition in aged skeletal muscle.American journal of physiology. Cell physiology · 2013Article
- Role of pericytes in skeletal muscle regeneration and fat accumulation.Stem cells and development · 2013Article
- Nuclear tropomyosin and troponin in striated muscle: new roles in a new locale?Journal of muscle research and cell motility · 2013Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Troponin T (TnT) plays a major role in striated muscle contraction. We recently demonstrated that the fast skeletal muscle TnT3 isoform is localized in the muscle nucleus, and either its full-length or COOH-terminus leads to muscle cell apoptosis. Here, we further explored the mechanism by which it enters the nucleus and promotes cytotoxicity. Amino acid truncation and substitution showed that its COOH-terminus contains a dominant nuclear/nucleolar localization sequence (KLKRQK) and the basic lysine and arginine residues might play an important role in the nuclear retention and nucleolar enrichment of KLKRQK-DsRed fusion proteins. Deleting this domain or substituting lysine and arginine residues (KLAAQK) resulted in a dramatic loss of TnT3 nuclear and nucleolar localization. In contrast, the GATAKGKVGGRWK domain-DsRed construct localized exclusively in the cytoplasm, indicating that a nuclear exporting sequence is possibly localized in this region. Additionally, we identified a classical DNA-binding leucine zipper domain (LZD) which is conserved among TnT isoforms and species. Deletion of LZD or KLKRQK sequence significantly reduced cell apoptosis compared to full-length TnT3. We conclude that TnT3 contains both a nuclear localization signal and a DNA-binding domain, which may mediate nuclear/nucleolar signaling and muscle cell apoptosis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.