ArticleThe Journal of biological chemistry2011
Down-regulation of the tumor suppressor C-terminal Src kinase (Csk)-binding protein (Cbp)/PAG1 is mediated by epigenetic histone modifications via the mitogen-activated protein kinase (MAPK)/phosphatidylinositol 3-kinase (PI3K) pathway.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 33 citations in OpenAlex.
- Article
- CSK-mediated signalling by integrins in cancer.Frontiers in cell and developmental biology · 2023Review
- Mechanisms of gene regulation by histone degradation in adaptation of yeast: an overview of recent advances.Archives of microbiology · 2022Review
- Src Family Tyrosine Kinases in Intestinal Homeostasis, Regeneration and Tumorigenesis.Cancers · 2020Review
- Review
- Dual Src Kinase/Pretubulin Inhibitor KX-01, Sensitizes ERα-negative Breast Cancers to Tamoxifen through ERα Reexpression.Molecular cancer research : MCR · 2017Article
- Article
- Cell-cycle-independent transitions in temporal identity of mammalian neural progenitor cells.Nature communications · 2016Article
- Histone deacetylase 3 expression correlates with vasculogenic mimicry through the phosphoinositide3-kinase / ERK-MMP-laminin5γ2 signaling pathway.Cancer science · 2015Article
- Hepatitis B virus X protein induces expression of alpha-fetoprotein and activates PI3K/mTOR signaling pathway in liver cells.Oncotarget · 2015Article
- Overexpression of Csk-binding protein decreases growth, invasion, and migration of esophageal carcinoma cells by controlling Src activation.World journal of gastroenterology · 2015Article
- PAG--a multipurpose transmembrane adaptor protein.Oncogene · 2014Review
- GRIM-19 mutations fail to inhibit v-Src-induced oncogenesis.Oncogene · 2014Article
- Article
- Histone deacetylases as targets for treatment of multiple diseases.Clinical science (London, England : 1979) · 2013Review
- PAG/Cbp suppression reveals a contribution of CTLA-4 to setting the activation threshold in T cells.Cell communication and signaling : CCS · 2013Article
- Regulation of u-PAR gene expression by H2A.Z is modulated by the MEK-ERK/AP-1 pathway.Nucleic acids research · 2012Article
- Regulation of the SRC family kinases by Csk.International journal of biological sciences · 2012Review
- Oncogenic signaling by tyrosine kinases of the SRC family in advanced colorectal cancer.American journal of cancer research · 2012Article
- Article
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5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The transmembrane adaptor protein Cbp (or PAG1) functions as a suppressor of Src-mediated tumor progression by promoting the inactivation of Src. The expression of Cbp is down-regulated in Src-transformed cells and in various human cancer cells, suggesting a potential role for Cbp as a tumor suppressor. However, the mechanisms underlying the down-regulation of Cbp remain unknown. The present study shows that Cbp expression is down-regulated by epigenetic histone modifications via the MAPK/PI3K pathway. In mouse embryonic fibroblasts, transformation by oncogenic Src and Ras induced a marked down-regulation of Cbp expression. The levels of Cbp expression were inversely correlated with the activity of MEK and Akt, and Cbp down-regulation was suppressed by inhibiting MEK and PI3K. Src transformation did not affect the stability of Cbp mRNA, the transcriptional activity of the cbp promoter, or the DNA methylation status of the cbp promoter CpG islands. However, Cbp expression was restored by treatment with histone deacetylase (HDAC) inhibitors and by siRNA-mediated knockdown of HDAC1/2. Src transformation significantly decreased the acetylation levels of histone H4 and increased the trimethylation levels of histone H3 lysine 27 in the cbp promoter. EGF-induced Cbp down-regulation was also suppressed by inhibiting MEK and HDAC. Furthermore, the inhibition of MEK or HDAC restored Cbp expression in human cancer cells harboring Cbp down-regulation through promoter hypomethylation. These findings suggest that Cbp down-regulation is primarily mediated by epigenetic histone modifications via oncogenic MAPK/PI3K pathways in a subset of cancer cells.
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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.