ArticleCell death & disease2016
praja2 regulates KSR1 stability and mitogenic signaling.
Article in Cell death & disease, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 53 citations in OpenAlex.
- Reshaping cancer cell plasticity by P-body dynamics and protein translation.Communications biology · 2026Review
- Aberrant PJA2-CHRM3 signaling creates a therapeutic vulnerability in gastric tumor.British journal of cancer · 2025Article
- PJA2 Suppresses Colorectal Cancer Progression by Controlling HDAC2 Degradation and Stability.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- ZC3H13 promotes autophagy in bladder cancer through m6A methylation modification of PJA2 and ubiquitination of KSR1.Human cell · 2024Article
- Proteomic profiling of prostate cancer reveals molecular signatures under antiandrogen treatment.Clinical proteomics · 2024Article
- Proximal protein landscapes of the type I interferon signaling cascade reveal negative regulation by PJA2.Nature communications · 2024Article
- Development of Genetically Encoded Fluorescent KSR1-Based Probes to Track Ceramides during Phagocytosis.International journal of molecular sciences · 2024Article
- Downregulation of praja2 restrains endocytosis and boosts tyrosine kinase receptors in kidney cancer.Communications biology · 2024Article
- Functional Divergence and Origin of the Vertebrate Praja Family.Journal of molecular evolution · 2024Article
- Ubiquitylation of BBSome is required for ciliary assembly and signaling.EMBO reports · 2023Article
- Identification of hub genes in bladder cancer based on weighted gene co-expression network analysis from TCGA database.Cancer reports (Hoboken, N.J.) · 2022Article
- Targeted inhibition of ubiquitin signaling reverses metabolic reprogramming and suppresses glioblastoma growth.Communications biology · 2022Article
- Interactome Analysis of Human Phospholipase D and Phosphatidic Acid-Associated Protein Network.Molecular & cellular proteomics : MCP · 2022Article
- m6A demethylase FTO suppresses pancreatic cancer tumorigenesis by demethylatingMolecular therapy. Nucleic acids · 2021Article
- ELK4 promotes the development of gastric cancer by inducing M2 polarization of macrophages through regulation of the KDM5A-PJA2-KSR1 axis.Journal of translational medicine · 2021Article
- The TBC1D31/praja2 complex controls primary ciliogenesis through PKA-directed OFD1 ubiquitylation.The EMBO journal · 2021Article
- Article
- Combination Design of Time-Dependent Magnetic Field and Magnetic Nanocomposites to Guide Cell Behavior.Nanomaterials (Basel, Switzerland) · 2020Article
- Photocrosslinking Activity-Based Probes for Ubiquitin RING E3 Ligases.Cell chemical biology · 2020Article
- Mitochondrial Homeostasis and Signaling in Parkinson's Disease.Frontiers in aging neuroscience · 2020Article
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 3 countries.
Funding
Abstract
The kinase suppressor of Ras 1 (KSR1) has a fundamental role in mitogenic signaling by scaffolding components of the Ras/MAP kinase pathway. In response to Ras activation, KSR1 assembles a tripartite kinase complex that optimally transfers signals generated at the cell membrane to activate ERK. We describe a novel mechanism of ERK attenuation based on ubiquitin-dependent proteolysis of KSR1. Stimulation of membrane receptors by hormones or growth factors induced KSR1 polyubiquitination, which paralleled a decline of ERK1/2 signaling. We identified praja2 as the E3 ligase that ubiquitylates KSR1. We showed that praja2-dependent regulation of KSR1 is involved in the growth of cancer cells and in the maintenance of undifferentiated pluripotent state in mouse embryonic stem cells. The dynamic interplay between the ubiquitin system and the kinase scaffold of the Ras pathway shapes the activation profile of the mitogenic cascade. By controlling KSR1 levels, praja2 directly affects compartmentalized ERK activities, impacting on physiological events required for cell proliferation and maintenance of embryonic stem cell pluripotency.
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Registered trials
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.