TY - JOUR
T1 - TRα2—An Untuned Second Fiddle or Fine‐Tuning Thyroid Hormone Action?
AU - Hönes, Georg Sebastian
AU - Härting, Nina
AU - Mittag, Jens
AU - Kaiser, Frank J.
N1 - Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2022/7/1
Y1 - 2022/7/1
N2 - Thyroid hormones (THs) control a wide range of physiological functions essential for me-tabolism, growth, and differentiation. On a molecular level, TH action is exerted by nuclear receptors (TRs), which function as ligand‐dependent transcription factors. Among several TR isoforms, the function of TRα2 remains poorly understood as it is a splice variant of TRα with an altered C‐ terminus that is unable to bind T3. This review highlights the molecular characteristics of TRα2, proposed mechanisms that regulate alternative splicing and indications pointing towards an antag-onistic function of this TR isoform in vitro and in vivo. Moreover, remaining knowledge gaps and major challenges that complicate TRα2 characterization, as well as future strategies to fully uncover its physiological relevance, are discussed.
AB - Thyroid hormones (THs) control a wide range of physiological functions essential for me-tabolism, growth, and differentiation. On a molecular level, TH action is exerted by nuclear receptors (TRs), which function as ligand‐dependent transcription factors. Among several TR isoforms, the function of TRα2 remains poorly understood as it is a splice variant of TRα with an altered C‐ terminus that is unable to bind T3. This review highlights the molecular characteristics of TRα2, proposed mechanisms that regulate alternative splicing and indications pointing towards an antag-onistic function of this TR isoform in vitro and in vivo. Moreover, remaining knowledge gaps and major challenges that complicate TRα2 characterization, as well as future strategies to fully uncover its physiological relevance, are discussed.
UR - http://www.scopus.com/inward/record.url?scp=85132431646&partnerID=8YFLogxK
U2 - 10.3390/ijms23136998
DO - 10.3390/ijms23136998
M3 - Scientific review articles
C2 - 35806002
AN - SCOPUS:85132431646
SN - 1661-6596
VL - 23
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 13
M1 - 6998
ER -