Regulation of STATs by Posttranslational Modifications

Decker, Thomas; Müller, Mathias; Kovarik, Pavel

doi:10.1007/978-94-017-3000-6_14

Cited by 3 publications

(8 citation statements)

References 75 publications

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“…39,40 (42)), and CaMKII and IKK⑀ (Stat1 (39, 40, 43)). A role for these kinases has however only been confirmed by gene knock-out or knockdown in a limited number of cases.…”

Section: Stat Modificationsmentioning

confidence: 99%

“…However, these mutants appear to regulate transcription by squelching other transcription factors like NFB. Additional studies suggest that some Stat1-dependent apoptotic responses require phosphorylation of Ser 727 but not tyrosine (40).…”

Section: Stat Modificationsmentioning

confidence: 99%

“…Many of these TADs contain conserved serine phosphorylation sites that direct the recruitment of coactivators, e.g. CBP or MCM (mini-chromosome maintenance) complex (40,54). Another regulatory role for the STAT TADs appears to be protein stability, as several STATs, including Stats 4 -6, can be targeted for ubiquitin-dependent destruction, whereas Stats 1-3 are considerably more stable (32,41).…”

Section: Stat Transcriptional Activationmentioning

confidence: 99%

See 2 more Smart Citations

JAK-STAT Signaling: From Interferons to Cytokines

Schindler

Levy

Decker

2007

Journal of Biological Chemistry

Self Cite

1,113

899

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50 years ago Isaacs and Lindenmann (1) first described interferons (IFNs) 2 as founding members of the cytokine family. Over the next 25 years, these and several other four-helix bundle cytokines were characterized. The subsequent 25 years witnessed an exponential growth in number of four-helix bundle cytokines and their corresponding receptors.The early availability of recombinant IFNs afforded an opportunity to investigate how cytokines induce gene expression, culminating in the identification of the JAK-STAT signaling paradigm (see Fig. 1). Subsequent studies identified 7 STATs and 4 JAKs, providing important insight into how the ϳ50 members of the four-helix bundle cytokine family transduce their potent biological responses. This review will briefly summarize this signaling paradigm (reviewed in Refs. 2-5) and then focus on STAT-dependent transcription.

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“…39,40 (42)), and CaMKII and IKK⑀ (Stat1 (39, 40, 43)). A role for these kinases has however only been confirmed by gene knock-out or knockdown in a limited number of cases.…”

Section: Stat Modificationsmentioning

confidence: 99%

Section: Stat Modificationsmentioning

confidence: 99%

Section: Stat Transcriptional Activationmentioning

confidence: 99%

See 1 more Smart Citation

JAK-STAT Signaling: From Interferons to Cytokines

Schindler

Levy

Decker

2007

Journal of Biological Chemistry

Self Cite

1,113

899

View full text Add to dashboard Cite

show abstract

“…However, for each specific STAT, except Stat2, this sequence is conserved in humans and mice [46, 70]. Many TADs include conserved serine phosphorylation sites that facilitate the recruitment of coactivators (e.g., CBP, p300 and the MCM complex; see below; [71, 72]). STAT TADs also recruit pol II, HATs (e.g., PCAF, GCN5 and NcoA-1 [73–75]), chromatin modifying complexes (e.g., BAF and SWI2-SNF2; [76–79]) and HDACs [80, 81].…”

Section: The Stat Family Of Transcription Factorsmentioning

confidence: 99%

“…With the potential exception of Stat2, all STATs are phosphorylated on at least one serine residue in their TAD, a modification that promotes transcriptional activity (see above; [71, 72, 124, 142, 143]. However, it is not clear where this modification occurs.…”

Section: Regulating Stat Activitymentioning

confidence: 99%

Inteferons pen the JAK–STAT pathway

Schindler

Plumlee

2008

Seminars in Cell & Developmental Biology

225

198

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Characterization of how IFNs mediate their biological response led to identification of the JAK-STAT signaling cascade, where JAKs are receptor-associated kinases and STATs the transcription factors they activate. Today, 4 JAKs and 7 STATs are known to transduce pivotal signals for the over 50 members of the four helix bundle family of cytokines. This review will provide an overview and historical perspective of the JAK-STAT paradigm.

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Mutational analysis reveals separable DNA binding and trans-activation of Drosophila STAT92E

Karsten

Plischke

Perrimon

et al. 2006

Cellular Signalling

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In the canonical model of JAK/STAT signalling STAT transcription factors are activated by JAK mediated tyrosine phosphorylation following pathway stimulation by external cytokines. Activated STAT molecules then homo- or heterodimerise before translocating to the nucleus where they bind to DNA sequences within the promoters of pathway target genes. DNA-bound STAT dimers then activate transcription of their targets via interaction with components of the basal transcription machinery. Here we describe a missense mutation in the SH2 domain of the single Drosophila STAT92E homologue which results in an amino-acid substitution conserved in both the canonical SH2 domain and STAT-like molecules previously identified in C. elegans and the mosquito Anopheles gambiae. This mutation leads to nuclear accumulation and constitutive DNA binding of Drosophila STAT92E even in the absence of JAK stimulation. Strikingly, this mutant shows only limited transcriptional activity in tissue culture based assays and functions as a dominant-negative at both the phenotypic and molecular levels in vivo. These features represent aspects of both dominant gain-of-function and dominant-negative activities and imply that the functions of DNA binding can be functionally separated from the role of STAT92E as a transcriptional activator. It is thus possible that an alternative post-translational modification, in addition to tyrosine phosphorylation, may be required to allow STAT to act as a transcriptional activator and suggests the existence of an alternative mechanism by which STAT transcriptional activity may be regulated in vivo.

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Regulation of STATs by Posttranslational Modifications

Cited by 3 publications

References 75 publications

JAK-STAT Signaling: From Interferons to Cytokines

JAK-STAT Signaling: From Interferons to Cytokines

Inteferons pen the JAK–STAT pathway

Mutational analysis reveals separable DNA binding and trans-activation of Drosophila STAT92E

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