P300 binds to and acetylates MTA2 to promote colorectal cancer cells growth

Zhou, Jun; Zhan, Songhua; Tan, Weihan; Cheng, Ruixin; Gong, Huan; Zhu, Quangang

doi:10.1016/j.bbrc.2014.01.062

Cited by 24 publications

(17 citation statements)

References 19 publications

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“…A recent study provided evidence that p300 is important for tumor cell growth and migration (20). In the present study, it was observed that knockdown of p300 significantly inhibited the migration and invasiveness of CNE-2 cells.…”

Section: Discussionmentioning

confidence: 99%

P300 promotes migration, invasion and epithelial-mesenchymal transition in a nasopharyngeal carcinoma cell line

et al. 2016

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A previous study demonstrated that p300 is overexpressed in nasopharyngeal carcinoma (NPC), and that its expression is an independent prognostic factor. The aim of the present study is to investigate the role of p300 in human NPC development. A small hairpin (sh) RNA lentiviral expression vector targeting the p300 gene was constructed to suppress the expression of p300 in NPC cells. Knockdown of p300 was verified by reverse transcription-quantitative polymerase chain reaction and western blotting. Wound-healing, invasion, immunofluorescence and immunoprecipitation assays were performed to assess the influence of p300 on nasopharyngeal tumorigenesis and metastasis in vitro. The expression of p300 was upregulated in NPC cell lines. After knockdown of p300, the migration and invasion ability of shp300 cells were significantly inhibited (P<0.05). Furthermore, the depletion of p300 expression in NPC cell lines resulted in the upregulation of epithelial phenotype marker E-cadherin and α-catenin, and downregulation of mesenchymal phenotype markers N-cadherin and vimentin. p300 promotes epithelial-mesenchymal transition (EMT) through the acetylation of Smad2 and Smad3 in the tumor growth factor-β signaling pathway. In conclusion, p300 may be involved in the invasion and metastasis of NPC through the induction of EMT.

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Section: Discussionmentioning

confidence: 99%

P300 promotes migration, invasion and epithelial-mesenchymal transition in a nasopharyngeal carcinoma cell line

et al. 2016

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“…Most of our current understanding of MTA’s PTM is derived from the work on MTA1 which is subjected to acetylation at lysine 626, ubiquitination at lysine 182 and lysine 626, SUMOylation at lysine 509, and methylation at lysine 532 (Ohshiro et al, 2010; Li et al, 2009b; Cong et al, 2011; Nair et al, 2013). The MTA2 protein is acetylated at lysine 152 by p300 histone acetylase enzyme (Zhou et al, 2014). In addition, functions of MTA proteins are influenced by the ability of MTA 1 and MTA2 to interact with histone H3 and chromatin remodeling components (Nair, et al, 2013; Wu et al, 2013).…”

Section: Basis Of Functionality Of Mta Proteinsmentioning

confidence: 99%

“…The functionality of MTA1 and MTA2 proteins is profoundly affected by their acetylation status by histone acetylase p300 (Ohshiro et al, 2010, Zhou et al, 2014). The RING-finger ubiquitin-protein ligase COP1 regulates the level of MTA1 protein by controlling its degradation via the ubiquitin-proteasome pathway in the context of DNA damage response (Li et al, 2009b); and MTA1 stability is modulated by its physical association with the tumor suppressor protein ARF (Li et al, 2011).…”

Section: Regulation Of Expression Of Mta Genesmentioning

confidence: 99%

Structure, expression and functions of MTA genes

Kumar

Wang

2016

Gene

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Metastatic associated proteins (MTA) are integrators of upstream regulatory signals with the ability to act as master coregulators for modifying gene transcriptional activity. The MTA family includes three genes and multiple alternatively spliced variants. The MTA proteins neither have their own enzymatic activity nor have been shown to directly interact with DNA. However, MTA proteins interact with a variety of chromatin remodeling factors and complexes with enzymatic activities for modulating the plasticity of nucleosomes, leading to the repression or derepression of target genes or other extra-nuclear and nucleosome remodeling and histone deacetylase (NuRD)-complex independent activities. The functions of MTA family members are driven by the steady state levels and subcellular localization of MTA proteins, the dynamic nature of modifying signals and enzymes, the structural features and post-translational modification of protein domains, interactions with binding proteins, and the nature of the engaged and resulting features of nucleosomes in the proximity of target genes. In general, MTA1 and MTA2 are the most upregulated genes in human cancer and correlate well with aggressive phenotypes, therapeutic resistance, poor prognosis and ultimately, unfavorable survival of cancer patients. Here we will discuss the structure, expression and functions of the MTA family of genes in the context of cancer cells.

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“…These findings suggest that acetylated MTA1 may have a broader significance in ER-positive breast cancer. Similar to MTA1, the MTA2 also undergoes acetylation on lysine 152 by p300 HAT [36]. The acetylation of MTA2 impacts its tumorigenic potential, as an acetylation inactive MTA2 mutant inhibits the growth of colorectal cancer cells.…”

Section: Mta1’s Mechanism Of Action In Cancer Cellsmentioning

confidence: 99%

Role of MTA1 in cancer progression and metastasis

Sen

Gui

Kumar

2014

Cancer Metastasis Rev

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The MTA1 protein contributes to the process of cancer progression and metastasis through multiple genes and protein targets and interacting proteins with roles in transformation, anchorage-independent growth, invasion, survival, DNA-repair, angiogenesis, hormone-independence, metastasis and therapeutic resistance. MTA proteins control a spectrum of cancer promoting processes by modulating the expression of target genes and/or the activity of MTA-interacting proteins. In the case of MTA1, these functions are manifested through post-translational modifications of MTA1 in response to upstream signals, MTA1 interaction with binding proteins and the expression of target gene products. The MTA1 coregulator interacts with nucleosomes through modified histones and is an integrator of extracellular signaling and gene activator. Studies delineating the molecular basis of dual functionality of MTA1 reveal that the functions of MTA1-chromatin modifying complexes in the context of target gene regulation are dynamic in nature. The nature and targets of MTA1-chromatin modifying complexes are also governed by the dynamic plasticity of the nucleosome landscape as well as kinetics of activation and inactivation of enzymes responsible for post-translational modifications on the MTA1 protein. These broadly applicable functions also explain why MTA1 may be a ‘hub’ gene, whose current understanding is limited to selective influences on gene with roles in cancer but further research may reveal a more global influence. Because the deregulation of enzymes and their substrates with roles in MTA1-biology is not necessarily limited to cancer, we speculate that the lessons from MTA1 as a prototype dual master coregulator will be relevant for other human diseases. In this context, the concept of the dynamic nature of corepressor versus coactivator complexes and the MTA1 proteome as a function of time to signal is likely to be generally applicable to other multi-proteins regulatory complexes in living systems.

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P300 binds to and acetylates MTA2 to promote colorectal cancer cells growth

Cited by 24 publications

References 19 publications

P300 promotes migration, invasion and epithelial-mesenchymal transition in a nasopharyngeal carcinoma cell line

P300 promotes migration, invasion and epithelial-mesenchymal transition in a nasopharyngeal carcinoma cell line

Structure, expression and functions of MTA genes

Role of MTA1 in cancer progression and metastasis

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