Sustained but Decoyed Activation of the JAK1-STAT Pathway by Aberrant Protein Aggregation Exacerbates Proteotoxicity

  • Circulation. 2024 Oct 15;150(16):1302-1305. doi: 10.1161/CIRCULATIONAHA.124.070067.
Mingqi Cai  1 ,  Bo Pan  1 ,  Peng Xiao  1 ,  Mark Bouska  1 ,  Megan T Lewno  1 ,  Yu Xing  2 ,  Erliang Zeng  3 ,  Huiyun Liang  4 ,  Faqian Li  4  5 ,  Xiang Gao  6 ,  Xuejun Wang  1
Affiliations
  • 1. Division of Basic Biomedical Sciences, University of South Dakota Sanford School of Medicine, Vermillion (M.C., B.P., P.X., M.B., M.T.L., X.W.).
  • 2. Department of Computer Science, Loyola University Chicago, IL (Y.X.).
  • 3. Division of Biostatistics and Computational Biology, University of Iowa College of Dentistry, Iowa City (E.Z.).
  • 4. Department of Pathology and Laboratory Medicine, Joe R. and Teresa Lozano Long School of Medicine, University of Texas Health Science Center at San Antonio (H.L., F.L.).
  • 5. Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis (F.L.).
  • 6. Department of Medicine, Stritch School of Medicine, Loyola University Chicago, Maywood, IL (X.G.).
PMID: 39401278 DOI: 10.1161/CIRCULATIONAHA.124.070067
Abstract

Aberrant protein aggregation hijacks phosphorylated STATs and decoys the JAK1-STAT pathway to exacerbate proteotoxicity.

Keywords
Janus kinase 1; Janus kinase inhibitors; STAT transcription factors; proteasome endopeptidase complex; protein aggregation, pathological; proteostasis deficiencies; ubiquitin.
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