Journal article
Exocyst protein subnetworks integrate Hippo and mTOR signaling to promote virus detection and cancer
Cell reports (Cambridge), Vol.36(5), pp.109491-109491
08/03/2021
DOI: 10.1016/j.celrep.2021.109491
PMCID: PMC8383154
PMID: 34348154
Abstract
The exocyst is an evolutionarily conserved protein complex that regulates vesicular trafficking and scaffolds signal transduction. Key upstream components of the exocyst include monomeric RAL GTPases, which help mount cell-autonomous responses to trophic and immunogenic signals. Here, we present a quantitative proteomics-based characterization of dynamic and signal-dependent exocyst protein interactomes. Under viral infection, an Exo84 exocyst subcomplex assembles the immune kinase Protein Kinase R (PKR) together with the Hippo kinase Macrophage Stimulating 1 (MST1). PKR phosphorylates MST1 to activate Hippo signaling and inactivate Yes Associated Protein 1 (YAP1). By contrast, a Sec5 exocyst subcomplex recruits another immune kinase, TANK binding kinase 1 (TBK1), which interacted with and activated mammalian target of rapamycin (mTOR). RALB was necessary and sufficient for induction of Hippo and mTOR signaling through parallel exocyst subcomplex engagement, supporting the cellular response to virus infection and oncogenic signaling. This study highlights RALB-exocyst signaling subcomplexes as mechanisms for the integrated engagement of Hippo and mTOR signaling in cells challenged by viral pathogens or oncogenic signaling.
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•Exocyst protein subcomplexes impart phenotypic specificity•Exo84 exocyst contains PKR/MST1, activating Hippo signaling•Sec5 exocyst contains TBK1/mTOR, activating mTOR signaling•Cancer cells can coopt these subcomplexes for cellular survival
Zaman et al. demonstrate that distinct exocyst subcomplexes modulate a RALB-mediated antiviral response. The authors identify PKR/MST1 interactions in an Exo84 subcomplex and TBK1/mTOR interactions in a Sec5 subcomplex, leading to engagement of Hippo and mTOR signaling, respectively, in pathogenic contexts, such as virus infection and cancer.
Details
- Title: Subtitle
- Exocyst protein subnetworks integrate Hippo and mTOR signaling to promote virus detection and cancer
- Creators
- Aubhishek Zaman - The University of Texas Southwestern Medical CenterXiaofeng Wu - The University of Texas Southwestern Medical CenterAndrew Lemoff - The University of Texas Southwestern Medical CenterSivaramakrishna Yadavalli - The University of Texas Southwestern Medical CenterJeon Lee - The University of Texas Southwestern Medical CenterChensu Wang - The University of Texas Southwestern Medical CenterJonathan Cooper - The University of Texas Southwestern Medical CenterElizabeth A. McMillan - The University of Texas Southwestern Medical CenterCharles Yeaman - University of IowaHamid Mirzaei - The University of Texas Southwestern Medical CenterMichael A. White - The University of Texas Southwestern Medical CenterTrever G. Bivona - UCSF Helen Diller Family Comprehensive Cancer Center
- Resource Type
- Journal article
- Publication Details
- Cell reports (Cambridge), Vol.36(5), pp.109491-109491
- Publisher
- Elsevier Inc
- DOI
- 10.1016/j.celrep.2021.109491
- PMID
- 34348154
- PMCID
- PMC8383154
- ISSN
- 2211-1247
- eISSN
- 2211-1247
- Language
- English
- Date published
- 08/03/2021
- Academic Unit
- Anatomy and Cell Biology; Internal Medicine
- Record Identifier
- 9984284456402771
Metrics
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