Targeting SOCS Proteins to Control JAK-STAT Signalling in Disease

Durham, Gillian A.; Williams, Jamie J.L.; Nasim, Talat; Palmer, Timothy M.

doi:10.1016/j.tips.2019.03.001

Cited by 116 publications

(86 citation statements)

References 58 publications

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“…Several approaches to reduce STAT3 activity have been proposed and include targeting of specific receptors or receptor-associated kinases, especially JAKs, upstream of STAT3, in addition to strategies to directly interfere with STAT3 activity by preventing its recruitment to receptors, dimerization, nuclear localization, and DNA binding [see Bharadwaj et al (2016b)]. Other approaches currently underway involve modulation of autoregulators of STAT3 activity, such as strategies to activate protein phosphatases, members of the protein inhibitors of activated STAT family, or suppressor of cytokine signaling (SOCS) protein members (Heppler and Frank, 2017;Durham et al, 2019).…”

Section: B Strategies To Target Signal Transducer and Activator Of Tmentioning

confidence: 99%

Targeting Janus Kinases and Signal Transducer and Activator of Transcription 3 to Treat Inflammation, Fibrosis, and Cancer: Rationale, Progress, and Caution

et al. 2020

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Section: B Strategies To Target Signal Transducer and Activator Of Tmentioning

confidence: 99%

Targeting Janus Kinases and Signal Transducer and Activator of Transcription 3 to Treat Inflammation, Fibrosis, and Cancer: Rationale, Progress, and Caution

et al. 2020

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“…SOCS1 (Suppressor Of Cytokine Signaling-1) is a member of the SOCS family comprising 8 members (SOCS1, 2, 3, 4, 5, 6, 7, and cytokine-inducible SH2 domain-containing protein (CISH)) which all contain an SH2 (Src Homology 2) domain and a SOCS box region [1][2][3]. Some members of the SOCS family (CISH, SOCS1, SOCS2 and SOCS3) are induced following JAK-STAT signaling activation and are also recognized retro-inhibitors of cytokine signaling (Cartoon: #1 and #2) [1][2][3]. We recently demonstrated that SOCS1 can be phosphorylated on tyrosine (Y)80 in its extended SH2 domain by members of the SRC family of non-receptor tyrosine kinases (SFKs) including YES1, SRC, LCK, LYN and BLK (Cartoon: #3) [4].…”

Section: Introductionmentioning

confidence: 99%

SOCS1: phosphorylation, dimerization and tumor suppression

et al. 2020

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Suppressor of cytokine signaling (SOCS) family members are upregulated following JAK-STAT pathway activation by cytokines. SOCS proteins are recognized inhibitors of cytokine signaling playing roles in cell growth and differentiation. Moreover, SOCS1 and SOCS3 have been shown to be involved in tumor suppression through their ability to interact with p53 leading to the activation of its transcriptional program and showing the implication of SOCS family members in the regulation of apoptosis, ferroptosis and senescence. More recently, we demonstrated that the SRC family of non-receptor tyrosine kinases (SFK) can phosphorylate SOCS1 leading to its homodimerization and inhibiting its interaction with p53. Then, we reactivated the SOCS1-p53 tumor suppressor axis with the SFK inhibitor dasatinib in combination with the p53 activating compound PRIMA. This work suggests new avenues for cancer treatment and leaves open several new questions that deserve to be addressed.

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“…SOCS1 and SOCS3 are the most extensively characterized members [9]. Several recent studies have revealed that some viruses could regulate expression of the host proteins by overstimulating SOCS1 and/or SOCS3, thereby inhibiting the immune signaling pathway and facilitating viral evasion of immune surveillance [10,11]. For instance, HIV infection interferes with the expression SOCS1 and SOCS3, leading to immune activation.…”

Section: Introductionmentioning

confidence: 99%

Induction of SOCS Expression by EV71 Infection Promotes EV71 Replication

Gao

Huang

Liu

et al. 2020

BioMed Research International

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Enterovirus 71 (EV71) is the causative pathogen of hand, foot, and mouth disease (HFMD). However, no effective antiviral therapy is currently available. Some viruses could escape the host’s innate immunity by upregulating suppressor of cytokine signaling (SOCS) proteins. Until now, whether EV71 evades the host immune system by regulating the expression of SOCS proteins remains unknown. In this study, we found that EV71 infection promoted SOCS expression at both mRNA and protein levels in vitro and in vivo. Consistently, the infectivity of EV71 was decreased significantly in the SOCS3 or SOCS1 knockdown cells, suggesting that SOCS1 and especially SOCS3 are crucial for EV71 infection. Further investigation showed that SOCS3 promoted virus infection by inhibiting interferon-induced STAT3 phosphorylation. SOCS1 and SOCS3 mRNA expressions were independent on virus-induced type I interferon expression but were blocked by the inhibitor of NF-κB. Therefore, EV71 infection stimulates the expression of SOCS proteins in an interferon-independent way and negatively regulates the JAK/STAT signaling pathway, thus escaping host immunity. All these results may add new information to the mechanism of EV71 in fighting against type I interferon responses.

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Targeting SOCS Proteins to Control JAK-STAT Signalling in Disease

Cited by 116 publications

References 58 publications

Targeting Janus Kinases and Signal Transducer and Activator of Transcription 3 to Treat Inflammation, Fibrosis, and Cancer: Rationale, Progress, and Caution

Targeting Janus Kinases and Signal Transducer and Activator of Transcription 3 to Treat Inflammation, Fibrosis, and Cancer: Rationale, Progress, and Caution

SOCS1: phosphorylation, dimerization and tumor suppression

Induction of SOCS Expression by EV71 Infection Promotes EV71 Replication

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