ArticleCell death and differentiation2020
Dual functions of Rack1 in regulating Hedgehog pathway.
Article in Cell death and differentiation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 17 citations in OpenAlex.
- RACK1 in host immune response to infections: molecular mechanisms and therapeutic potentials.Frontiers in immunology · 2026Review
- A Duality of Function: An Integrative Model of RACK1 as a Switch Between Translational and Signaling Hubs.International journal of molecular sciences · 2025Review
- Tai/NCOA2 suppresses the Hedgehog pathway by directly targeting the transcription factor Ci/GLI.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- The AAA-ATPase Ter94 regulates wing size in Drosophila by suppressing the Hippo pathway.Communications biology · 2024Article
- Molecular Cloning, Characterization, and Expression of a Receptor for Activated Protein Kinase C1 (RACK1) Gene inBiology · 2024Article
- Loss of SMURF2 expression enhances RACK1 stability and promotes ovarian cancer progression.Cell death and differentiation · 2023Article
- Neuroligin 2 governs synaptic morphology and function through RACK1-cofilin signaling in Drosophila.Communications biology · 2023Article
- RACK1 facilitates breast cancer progression by competitively inhibiting the binding of β-catenin to PSMD2 and enhancing the stability of β-catenin.Cell death & disease · 2023Article
- Usp8 promotes tumor cell migration through activating the JNK pathway.Cell death & disease · 2022Article
- Stabilization of CCDC102B by Loss of RACK1 Through the CMA Pathway Promotes Breast Cancer MetastasisFrontiers in oncology · 2022Article
- The Hh pathway promotes cell apoptosis through Ci-Rdx-Diap1 axis.Cell death discovery · 2021Article
- Tumour Microenvironment: Roles of the Aryl Hydrocarbon Receptor, O-GlcNAcylation, Acetyl-CoA and Melatonergic Pathway in Regulating Dynamic Metabolic Interactions across Cell Types-Tumour Microenvironment and Metabolism.International journal of molecular sciences · 2020Review
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hedgehog (Hh) pathway plays multiple roles in many physiological processes and its dysregulation leads to congenital disorders and cancers. Hh regulates the cellular localization of Smoothened (Smo) and the stability of Cubitus interruptus (Ci) to fine-tune the signal outputs. However, the underlying mechanisms are still unclear. Here, we show that the scaffold protein Rack1 plays dual roles in Hh signaling. In the absence of Hh, Rack1 promotes Ci and Cos2 to form a Ci-Rack1-Cos2 complex, culminating in Slimb-mediated Ci proteolysis. In the presence of Hh, Rack1 dissociates from Ci-Rack1-Cos2 complex and forms a trimeric complex with Smo and Usp8, leading to Smo deubiquitination and cell surface accumulation. Furthermore, we find the regulation of Rack1 on Hh pathway is conserved from Drosophila to mammalian cells. Our findings demonstrate that Rack1 plays dual roles during Hh signal transduction and provide Rack1 as a potential drug target for Hh-related diseases.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.