STRIPAK directs PP2A activity toward MAP4K4 to promote oncogenic transformation

Kim, Jong Wook; Berrios, Christian; Kim, Miju; Schade, Amy E.; Adelmant, Guillaume; Yeerna, Huwate; Damato, Emily; Iniguez, Amanda Balboni; Swanson, Selene K.; Florens, Laurence; Washburn, Michael P.; Stegmaier, Kim; Gray, N. A. B.; Tamayo, Pablo; Gjoerup, Ole; Marto, Jarrod A.; DeCaprio, James A.; Hahn, William C.

doi:10.1101/823096

Cited by 8 publications

(12 citation statements)

References 84 publications

(141 reference statements)

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“…STRIPAK is an evolutionarily conserved multiprotein complex that functionally links the phosphatase activity of PP2A to different Ste20-like kinases ( Gordon et al, 2011 ; Goudreault et al, 2009 ; Kim et al, 2020 ; Kück et al, 2019 ; Ribeiro et al, 2010 ; Shi et al, 2016 ). Both enzymatic functions are scaffolded by striatin proteins ( Fig.…”

Section: Resultsmentioning

confidence: 99%

STRIPAK regulates Slik localization to control mitotic morphogenesis and epithelial integrity

Jamblinne

Decelle

Dehghani

et al. 2020

Journal of Cell Biology

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Proteins of the ezrin, radixin, and moesin (ERM) family control cell and tissue morphogenesis. We previously reported that moesin, the only ERM in Drosophila, controls mitotic morphogenesis and epithelial integrity. We also found that the Pp1-87B phosphatase dephosphorylates moesin, counteracting its activation by the Ste20-like kinase Slik. To understand how this signaling pathway is itself regulated, we conducted a genome-wide RNAi screen, looking for new regulators of moesin activity. We identified that Slik is a new member of the striatin-interacting phosphatase and kinase complex (STRIPAK). We discovered that the phosphatase activity of STRIPAK reduces Slik phosphorylation to promote its cortical association and proper activation of moesin. Consistent with this finding, inhibition of STRIPAK phosphatase activity causes cell morphology defects in mitosis and impairs epithelial tissue integrity. Our results implicate the Slik–STRIPAK complex in the control of multiple morphogenetic processes.

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Section: Resultsmentioning

confidence: 99%

STRIPAK regulates Slik localization to control mitotic morphogenesis and epithelial integrity

Jamblinne

Decelle

Dehghani

et al. 2020

Journal of Cell Biology

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“…A recent study revealed that enteroblasts in Drosophila adult intestine sense the mechanical force generated by food congestion to modulate the Hippo signaling and stem cell activity by regulating the membrane association of Msn and its phosphorylation by Tao-1 ( Jiang, 2018 ; Li et al, 2018 ). Hpo/MST12 and MAP4Ks are negatively regulated by a large protein complex called STRIPAK that brings PP2A to dephosphorylate and inhibit these kinases ( Bae et al, 2017 ; Zheng et al, 2017 ; Kim J.W. et al, 2020 ; Seo et al, 2020 ; Tang et al, 2020 ).…”

Section: Overview Of the Canonical Hippo Signaling Pathwaymentioning

confidence: 99%

Hippo-Independent Regulation of Yki/Yap/Taz: A Non-canonical View

Cho

Jen

2021

Front. Cell Dev. Biol.

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Initially identified in Drosophila, the Hippo signaling pathway has emerged as an evolutionarily conserved tumor suppressor pathway that controls tissue growth and organ size by simultaneously inhibiting cell proliferation and promoting cell death. Deregulation of Hippo pathway activity has been implicated in a wide range of human cancers. The core Hippo pathway consists of a kinase cascade: an upstream kinase Hippo (Hpo)/MST1/2 phosphorylates and activates a downstream kinase Warts (Wts)/Lats1/2, leading to phosphorylation and inactivation of a transcriptional coactivator Yki/YAP/Taz. Many upstream signals, including cell adhesion, polarity, mechanical stress, and soluble factors, regulate Hippo signaling through the kinase cascade, leading to change in the cytoplasmic/nuclear localization of Yki/YAP/Taz. However, recent studies have uncovered other mechanisms that regulate Yki/YAP/Taz subcellular localization, stability, and activity independent of the Hpo kinase cascade. These mechanisms provide additional layers of pathway regulation, nodes for pathway crosstalk, and opportunities for pathway intervention in cancer treatment and regenerative medicine.

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“…The cBioPortal for Cancer Genomics (http://cbioportal.org) and The Human Protein Atlas dataset (www.proteinatlas.org) were used to explore, visualize, and analyze multidimensional cancer genomics data. These are open-access resources currently providing data from more than 5,000 tumor samples from 20 cancer studies (18)(19)(20). We also used datasets from The Cancer Genome Atlas (TCGA, https://www.cancer.gov/tcga) (21) and Gynecologic Tissue and Fluid Repository (22).…”

Section: Methodsmentioning

confidence: 99%

“…These resulting ssGSEA scores for individual samples were used for interpreting gene expression profiles using gene sets from the Molecular Signatures Database (MSigDB, www.msigdb.org) (26,27). In addition to the MSigDB gene sets, the YAP gene set used was derived from a previous study (20). To quantify the degree of association, an information-theoretic measure of information coefficient (IC) was calculated and an empirical permutation test for statistical significance calculations carried out against the expression of specific mRNAs (e.g.…”

Section: Methodsmentioning

confidence: 99%