Signal Integration and Gene Induction by a Functionally Distinct STAT3 Phosphoform

Waitkus, Matthew S.; Chandrasekharan, Unni M.; Willard, Belinda; Tee, Thomas L.; Hsieh, Jason K.; Przybycin, Christopher G.; Rini, Brian I.; DiCorleto, Paul E.

doi:10.1128/mcb.00034-14

Cited by 37 publications

(37 citation statements)

References 53 publications

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“…The emerging view now is that STAT3 plays the role of a signal integrator; this hypothesis is supported by the fact that STAT3 activity is modulated via myriad posttranslational modifications including tyrosine and serine phosphorylation, lysine acetylation, and lysine and arginine methylation and can respond to a wide variety of stimuli also shared by other signaling networks [203]. …”

Section: Stat3 and Integration Of Complex Signaling Networkmentioning

confidence: 99%

Contribution of STAT3 to Inflammatory and Fibrotic Diseases and Prospects for its Targeting for Treatment

Kasembeli

Bharadwaj

Robinson

et al. 2018

IJMS

146

119

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Signal transducer and activator of transcription (STAT) 3 plays a central role in the host response to injury. It is activated rapidly within cells by many cytokines, most notably those in the IL-6 family, leading to pro-proliferative and pro-survival programs that assist the host in regaining homeostasis. With persistent activation, however, chronic inflammation and fibrosis ensue, leading to a number of debilitating diseases. This review summarizes advances in our understanding of the role of STAT3 and its targeting in diseases marked by chronic inflammation and/or fibrosis with a focus on those with the largest unmet medical need.

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Section: Stat3 and Integration Of Complex Signaling Networkmentioning

confidence: 99%

Contribution of STAT3 to Inflammatory and Fibrotic Diseases and Prospects for its Targeting for Treatment

Kasembeli

Bharadwaj

Robinson

et al. 2018

IJMS

146

119

View full text Add to dashboard Cite

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“…Reversible acetylation on lysine residues in the SH2 domain (K 685 ) and in the NH2 terminus (K 49 , K 87 ) also promotes STAT3 dimer stabilization, DNA binding, interaction with transcriptional coactivators, and target gene expression [28–31]. Recently, a novel phospho-Threonine (pT 714 )/pS 727 form of STAT3 has been implicated in renal cell carcinoma [32]. Moreover, distinct roles for unphosphorylated STAT3 in oncogenesis and gene transcription have also been described [33].…”

Section: Stat3mentioning

confidence: 99%

“…Finally, STAT3 is also enhanced in the testes of cachexic Apc Min mice, as STAT3 increases with increasing cachexia severity and circulating IL-6, and concomitant with declining testis mass and testosterone levels [32]. Hypogonadism is frequently observed in cachectic states, particularly burn injury.…”

Section: 0 Stat3 Outside Muscle In Cachexiamentioning

confidence: 99%

STAT3 in the systemic inflammation of cancer cachexia

Zimmers

Fishel

Bonetto

2016

Seminars in Cell & Developmental Biology

194

166

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Weight loss is diagnostic of cachexia, a debilitating syndrome contributing mightily to morbidity and mortality in cancer. Most research has probed mechanisms leading to muscle atrophy and adipose wasting in cachexia; however cachexia is a truly systemic phenomenon. Presence of the tumor elicits an inflammatory response and profound metabolic derangements involving not only muscle and fat, but also the hypothalamus, liver, heart, blood, spleen and likely other organs. This global response is orchestrated in part through circulating cytokines that rise in conditions of cachexia. Exogenous Interleukin-6 (IL6) and related cytokines can induce most cachexia symptomatology, including muscle and fat wasting, the acute phase response and anemia, while IL-6 inhibition reduces muscle loss in cancer. Although mechanistic studies are ongoing, certain of these cachexia phenotypes have been causally linked to the cytokine-activated transcription factor, STAT3, including skeletal muscle wasting, cardiac dysfunction and hypothalamic inflammation. Correlative studies implicate STAT3 in fat wasting and the acute phase response in cancer cachexia. Parallel data in non-cancer models and disease states suggest both contributory and protective functions for STAT3 in other organs during cachexia. Finally, STAT3 contributes to cancer cachexia through enhancing tumorigenesis, metastasis and immune suppression, particularly in tumors associated with high prevalence of cachexia. This review examines the evidence linking STAT3 to multi-organ manifestations of cachexia in cancer and evidence for targeting STAT3 for anti-cachexia therapies.

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“…All members of the STAT family translocate to the cell nucleus once activated by phosphorylation where they act as transcriptional activators [88, 89]. STAT3 was first discovered in 1994 and is activated when phosphorylated at the Tyrosine 705 position [90, 91]. Following propofol exposure, pSTAT3 expression in the neurons was significantly reduced but was not altered following manipulation of miR-21 expression, suggesting that STAT3 may be an important upstream regulator of miR-21 in propofol-induced neurotoxicity [45].…”

Section: Micrornas and Anesthetic-induced Developmental Neurotoxicitymentioning

confidence: 99%

MicroRNAs: New Players in Anesthetic-Induced Developmental Neurotoxicity

Twaroski

Bošnjak

Bai³

2015

Pharm Anal Acta

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Growing evidence demonstrates that prolonged exposure to general anesthetics during brain development induces widespread neuronal cell death followed by long-term memory and learning disabilities in animal models. These studies have raised serious concerns about the safety of anesthetic use in pregnant women and young children. However, the underlying mechanisms of anesthetic-induced neurotoxicity are complex and are not well understood. MicroRNAs are endogenous, small, non-coding RNAs that have been implicated to play important roles in many different disease processes by negatively regulating target gene expression. A possible role for microRNAs in anesthetic-induced developmental neurotoxicity has recently been identified, suggesting that microRNA-based signaling might be a novel target for preventing the neurotoxicity. Here we provide an overview of anesthetic-induced developmental neurotoxicity and focus on the role of microRNAs in the neurotoxicity observed in both human stem cell-derived neuron and animal models. Aberrant expression of some microRNAs has been shown to be involved in anesthetic-induced developmental neurotoxicity, revealing the potential of microRNAs as therapeutic or preventive targets against the toxicity.

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Signal Integration and Gene Induction by a Functionally Distinct STAT3 Phosphoform

Cited by 37 publications

References 53 publications

Contribution of STAT3 to Inflammatory and Fibrotic Diseases and Prospects for its Targeting for Treatment

Contribution of STAT3 to Inflammatory and Fibrotic Diseases and Prospects for its Targeting for Treatment

STAT3 in the systemic inflammation of cancer cachexia

MicroRNAs: New Players in Anesthetic-Induced Developmental Neurotoxicity

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