ArticleCell reports2023
p120 RasGAP and ZO-2 are essential for Hippo signaling and tumor-suppressor function mediated by p190A RhoGAP.
Article in Cell reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 1 citations in OpenAlex.
- ZO-2 blocks the localization of PGAM5 protein to the mitochondrial membrane and suppresses pancreatic cancer malignancy through metabolic reprogramming.Genes & diseases · 2027Article
- Tight junction structure, assembly and (dys)function.Nature reviews. Molecular cell biology · 2026Review
- Fibrotic differentiation profile of skeletal and cardiac muscle fibroadipogenic progenitors in D2-mdx mouse.Journal of neuromuscular diseases · 2026Article
- Loss of p190A RhoGAP induces aneuploidy and enhances bladder cancer cell migration and invasion by modulating actin dynamics.Scientific reports · 2025Article
- Targeted long-read methylation analysis using hybridization capture suitable for clinical specimens.Cell reports methods · 2025Article
- Molecular alterations associated with pathophysiology in liver-specific ZO-1 and ZO-2 knockout mice.Cell structure and function · 2024Article
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
ARHGAP35, which encodes p190A RhoGAP (p190A), is a major cancer gene. p190A is a tumor suppressor that activates the Hippo pathway. p190A was originally cloned via direct binding to p120 RasGAP (RasGAP). Here, we determine that interaction of p190A with the tight-junction-associated protein ZO-2 is dependent on RasGAP. We establish that both RasGAP and ZO-2 are necessary for p190A to activate large tumor-suppressor (LATS) kinases, elicit mesenchymal-to-epithelial transition, promote contact inhibition of cell proliferation, and suppress tumorigenesis. Moreover, RasGAP and ZO-2 are required for transcriptional modulation by p190A. Finally, we demonstrate that low ARHGAP35 expression is associated with shorter survival in patients with high, but not low, transcript levels of TJP2 encoding ZO-2. Hence, we define a tumor-suppressor interactome of p190A that includes ZO-2, an established constituent of the Hippo pathway, and RasGAP, which, despite strong association with Ras signaling, is essential for p190A to activate LATS kinases.
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