期刊
FEBS JOURNAL
卷 289, 期 20, 页码 6235-6255出版社
WILEY
DOI: 10.1111/febs.16116
关键词
canonical; noncanonical; post-translational modification; STAT3; transcription factor
资金
- FEDER funds through COMPETE2020-Programa Operacional Competitividade e Internacionalizacao (POCI) [LISBOA-01-0145FEDER-007660]
- Fundacao para a Ciencia e Tecnologia (FCT) [UIDB/04046/2020, UIDP/04046/2020, IF/00094/2013/CP1173/CT0005, PTDC/MED-NEU/31417/2017]
- Fundação para a Ciência e a Tecnologia [IF/00094/2013/CP1173/CT0005, PTDC/MED-NEU/31417/2017] Funding Source: FCT
The STAT family of transcription factors is involved in various biological phenomena, but the complexity of their signaling pathways goes beyond the traditional model, while more than 80 post-translational modifications for STAT3 have functions that are not fully understood.
The Signal Transducer and Activator of Transcription (STAT) family of transcription factors is involved in inflammation, immunity, development, cancer, and response to injury, among other biological phenomena. Canonical STAT signaling is often represented as a 3-step pathway involving the sequential activation of a membrane receptor, an intermediate kinase, and a STAT transcription factor. The rate-limiting phosphorylation at a highly conserved C-terminal tyrosine residue determines the nuclear translocation and transcriptional activity of STATs. This apparent simplicity is actually misleading and can hardly explain the pleiotropic nature of STATs, the existence of various noncanonical STAT pathways, or the key role of the N-terminal domain in STAT functions. More than 80 post-translational modifications (PTMs) have been identified for STAT3, but their functions remain barely understood. Here, we provide a brief but comprehensive overview of these underexplored PTMs and their role on STAT3 canonical and noncanonical functions. A less tyrosine-centric point of view may be required to advance our understanding of STAT signaling.
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