ArticleThe Journal of biological chemistry2014
DNA damage induces the accumulation of Tiam1 by blocking β-TrCP-dependent degradation.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 18 citations in OpenAlex.
- Research Progress on the Functional Regulation Mechanisms of ZKSCAN3.Biomolecules · 2025Review
- Targeting Tiam1 Enhances Hippocampal-Dependent Learning and Memory in the Adult Brain and Promotes NMDA Receptor-Mediated Synaptic Plasticity and Function.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Molecular glue degrader for tumor treatment.Frontiers in oncology · 2024Review
- Zkscan3 affects erythroblast development by regulating the transcriptional activity of GATA1 and KLF1 in mice.Journal of molecular histology · 2022Article
- The Rac-GEF Tiam1 Promotes Dendrite and Synapse Stabilization of Dentate Granule Cells and Restricts Hippocampal-Dependent Memory Functions.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- Up-Regulation of Tiam1 Promotes the Radioresistance of Laryngeal Squamous Cell Carcinoma Through Activation of the JNK/ATF-2 Signaling Pathway.OncoTargets and therapy · 2020Article
- TIAM1 Antagonizes TAZ/YAP Both in the Destruction Complex in the Cytoplasm and in the Nucleus to Inhibit Invasion of Intestinal Epithelial Cells.Cancer cell · 2017Article
- The β-TrCP-FBXW2-SKP2 axis regulates lung cancer cell growth with FBXW2 acting as a tumour suppressor.Nature communications · 2017Article
- Deregulation of F-box proteins and its consequence on cancer development, progression and metastasis.Seminars in cancer biology · 2016Review
- GABARAP proteins as scaffolds in localized TIAM1-RAC1 signaling.Molecular & cellular oncology · 2016Article
- An EGFR/PI3K/AKT axis promotes accumulation of the Rac1-GEF Tiam1 that is critical in EGFR-driven tumorigenesis.Oncogene · 2015Article
- HUWE1 ubiquitylates and degrades the RAC activator TIAM1 promoting cell-cell adhesion disassembly, migration, and invasion.Cell reports · 2015Article
- Degradation of Tiam1 by casein kinase 1 and the SCFβTrCP ubiquitin ligase controls the duration of mTOR-S6K signaling.The Journal of biological chemistry · 2014Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Rac1/JNK cascade plays important roles in DNA damage-induced apoptosis. However, how this cascade is activated upon DNA damage remains to be fully understood. We show here that, in untreated cells, Tiam1, a Rac1-specific guanine nucleotide exchange factor, is phosphorylated by casein kinase 1 (CK1) at its C terminus, leading to Skp, Cullin, F-box-containing(β-TrCP) recognition, ubiquitination, and proteasome-mediated degradation. Upon DNA-damaging anticancer drug treatment, CK1/β-TrCP-mediated Tiam1 degradation is abolished, and the accumulated Tiam1 contributes to downstream activation of Rac1/JNK. Consistently, tumor cells overexpressing Tiam1 are hypersensitive to DNA-damaging drug treatment. In xenograft mice, Tiam1-high cells are more susceptible to doxorubicin treatment. Thus, our results uncover that inhibition of proteasome-mediated Tiam1 degradation is an upstream event leading to Rac1/JNK activation and cell apoptosis in response to DNA-damaging drug treatment.
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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.