Roles of CREB-binding protein (CBP)/p300 in respiratory epithelium tumorigenesis

Karamouzis, Michalis V.; Konstantinopoulos, Panagiotis A.; Papavassiliou, Athanasios G.

doi:10.1038/cr.2007.10

Cited by 74 publications

(54 citation statements)

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“…Thus, at least four HATs (TIP60, CBP, p300 and GCN5) are likely to have redundant roles in histone acetylation at DSB sites in human cells. HATs, including CBP and p300, also acetylate non-histone proteins (Karamouzis et al, 2007). Further study is needed to elucidate the NHEJ mechanisms facilitated by these HATs.…”

Section: Discussionmentioning

confidence: 99%

“…However, both CBP and p300 have a role during transcription, either as a physical bridge for diverse proteins, or as a scaffold for the formation of multicomponent complexes. In addition, acetylation of nonhistone proteins, such as p53, by CBP and p300 enhances their DNA-binding activity and regulates protein-DNA recognition (Karamouzis et al, 2007). Thus, the functions of CBP and p300, other than that of HATs, might also help the recruitment of KU70/80 proteins.…”

Section: Discussionmentioning

confidence: 99%

“…Using this system, we found that two HAT inhibitors, anacardic acid and curcumin, both known to radio-sensitize cancer cells (Khafif et al, 2005;Sun et al, 2006;Javvadi et al, 2008), suppress NHEJ of DSBs. The CBP and p300 proteins are homologous HATs, known to function as transcription co-activators, and their enzymatic activity is inhibited by anacardic acid and curcumin (Karamouzis et al, 2007). We showed that CBP and p300 function as histone H3 and H4 acetyltransferases at DSB sites during NHEJ, and facilitate the recruitment of KU70/80 proteins in cooperation with the SWI/SNF chromatin remodeling complex.…”

Section: Introductionmentioning

confidence: 91%

“…Recruitment of CBP and p300 to DSB sites Both CBP and p300 function as HATs during transcriptional regulation (Karamouzis et al, 2007). Ablation of CBP/p300 did not significantly affect the expression levels of NHEJ core proteins (Supplementary Figure S3), indicating that the suppression of NHEJ through ablation of CBP or p300 was caused by mechanisms other than the downregulation of proteins engaged in NHEJ.…”

Section: Suppression Of Nhej In Vivo By Ablation Of Cbp or P300mentioning

confidence: 99%

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Histone acetylation by CBP and p300 at double-strand break sites facilitates SWI/SNF chromatin remodeling and the recruitment of non-homologous end joining factors

Ogiwara¹,

et al. 2011

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Non-homologous end joining (NHEJ) is a major repair pathway for DNA double-strand breaks (DSBs) generated by ionizing radiation (IR) and anti-cancer drugs. Therefore, inhibiting the activity of proteins involved in this pathway is a promising way of sensitizing cancer cells to both radiotherapy and chemotherapy. In this study, we developed an assay for evaluating NHEJ activity against DSBs in chromosomal DNA in human cells to identify the chromatin modification/remodeling proteins involved in NHEJ. We showed that ablating the activity of the homologous histone acetyltransferases, CBP and p300, using inhibitors or small interfering RNAs-suppressed NHEJ. Ablation of CBP or p300 impaired IR-induced DSB repair and sensitized lung cancer cells to IR and the anti-cancer drug, etoposide, which induces DSBs that are repaired by NHEJ. The CBP/p300 proteins were recruited to sites of DSBs and their ablation suppressed acetylation of lysine 18 within histone H3, and lysines 5, 8, 12, and 16 within histone H4, at the DSB sites. This then suppressed the recruitment of KU70 and KU80, both key proteins for NHEJ, to the DSB sites. Ablation of CBP/p300 also impaired the recruitment of BRM, a catalytic subunit of the SWI/SNF complex involved in chromatin remodeling at DSB sites. These results indicate that CBP and p300 function as histone H3 and H4 acetyltransferases at DSB sites in NHEJ and facilitate chromatin relaxation. Therefore, inhibition CBP and p300 activity may sensitize cancer cells to radiotherapy and chemotherapy.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 91%

Section: Suppression Of Nhej In Vivo By Ablation Of Cbp or P300mentioning

confidence: 99%

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Histone acetylation by CBP and p300 at double-strand break sites facilitates SWI/SNF chromatin remodeling and the recruitment of non-homologous end joining factors

Ogiwara¹,

et al. 2011

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“…It was incubated with AA at different concentrations (0,5,25 and 125 μmol/L) at 30 ℃ and 5% CO 2 for 24 hours. The cells were digested with 2.5 g/L trypsase in a shaking bath.…”

Section: Detection Of Cell Cycles Using Flow Cytometrymentioning

confidence: 99%

Anacardic acid (6-pentadecylsalicylic acid) induces apoptosis of prostate cancer cells through inhibition of androgen receptor and activation of p53 signaling

Jing¹,

Tan²,

Binghai³

et al. 2012

Chin. J. Cancer Res.

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Anacardic acid (AA) is a mixture of 2-hydroxy-6-alkylbenzoic acid homologs. It is widely regarded as a non-specific histone acetyltransferase inhibitor of p300. The effects and the mechanisms of AA in LNCaP cells (prostate cancer cells) remain unknown. To investigate the effect of AA on LNCaP cells, we had carried out several experiments and found that AA inhibits LNCaP cell proliferation, induces G1/S cell cycle arrest and apoptosis of LNCaP cell. The mechanisms via which AA acts on LNCaP cells may be due to the following aspects. First, AA can regulate p300 transcription and protein level except for its mechanisms regulating function of p300 through post-translational modification in LNCaP cells. Second, AA can activate p53 through increasing the phosphorylation of p53 on Ser15 in LNCaP cells. AA can selectively activate p21 (target genes of p53). Third, AA can down-regulates androgen receptor (AR) through supressing p300. Our study suggests that AA has multiple anti-tumor activities in LNCaP cells and warrants further investigation. Chin J Cancer Res 2012;24(4):275-283 www.thecjcr.org culture medium when necessary. DMEM, growth factorreduced matrigel and fetalbovine serum (FBS) were bought from BD Corporation (San Jose, CA). The Lipofectamine™ 2000 and the Total RNA Extraction kit were purchased from Invitrogen (Carlsbad, CA). The MTT Cell Proliferation and Cytotoxicity Assay kit and the Annexin V-FITC & PI Apoptosis Detection kit were purchased from KeyGen Biotech (Nanjing, China). SYBR Green PCR Master Mix were purchased from Fermentas (Burlington, Ontario, Canada). The Total Protein Extraction kit was purchased from ProMab (Changsha, China). Primary antibodies for p300, p21, p53, AR, cyclin D1 and siRNA specifically for p300 were bought from Santa Cruz Biotechnology (Santa Cruz, CA). Primary antibody for phospho-p53 (Ser 15) was purchased from Cell Signaling Technology. RPMI 1640 was purchased from GIBCO. Cell lines and cell cultureLNCaP was purchased from Yinrun (Changsha, China). LNCaP is a classical metastatic prostate adenocarcinoma cell line, derived from metastatic lymph nodes. LNCaP was cultured with both RPMI 1640 and 10% FBS, and subcultured weekly (37 ℃, 5% CO 2 ). p300 siRNA transfectionT h e L n c a p c e l l s w e r e s e e d e d i n t o 6 -w e l l p l a t e s (4×10 4 -5×10 4 cells/well) and cultured in 2 mL basic culture medium containing 10% FBS overnight until the cells were 70% confluent. Cells were transiently transfected with a validated scrambled control siRNA, or p300 siRNA by using InterferinTM transfection reagent. The mixture of siRNA and InterferinTM transfection reagent was incubated for 10 min, added to each well of the 6-well plates and incubated at 37 ℃ for 24 h before drug treatment. Detecting the inhibition of cell growth using MTT assaysLncap cells were treated with AA or transfected with p300 siRNA before drug treatment. Cells were incubated at various concentrations (0, 5, 25, and 125 μmol/L) at a series of time points (0, 4, 24 and 28 h). Then, 5 mg/mL of MTT so...

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Cell fate regulation governed by p53: Friends or reversible foes in cancer therapy

Song,

Yang,

Zhang

2024

Cancer Communications

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Cancer is a leading cause of death worldwide. Targeted therapies aimed at key oncogenic driver mutations in combination with chemotherapy and radiotherapy as well as immunotherapy have benefited cancer patients considerably. Tumor protein p53 (TP53), a crucial tumor suppressor gene encoding p53, regulates numerous downstream genes and cellular phenotypes in response to various stressors. The affected genes are involved in diverse processes, including cell cycle arrest, DNA repair, cellular senescence, metabolic homeostasis, apoptosis, and autophagy. However, accumulating recent studies have continued to reveal novel and unexpected functions of p53 in governing the fate of tumors, for example, functions in ferroptosis, immunity, the tumor microenvironment and microbiome metabolism. Among the possibilities, the evolutionary plasticity of p53 is the most controversial, partially due to the dizzying array of biological functions that have been attributed to different regulatory mechanisms of p53 signaling. Nearly 40 years after its discovery, this key tumor suppressor remains somewhat enigmatic. The intricate and diverse functions of p53 in regulating cell fate during cancer treatment are only the tip of the iceberg with respect to its equally complicated structural biology, which has been painstakingly revealed. Additionally, TP53 mutation is one of the most significant genetic alterations in cancer, contributing to rapid cancer cell growth and tumor progression. Here, we summarized recent advances that implicate altered p53 in modulating the response to various cancer therapies, including chemotherapy, radiotherapy, and immunotherapy. Furthermore, we also discussed potential strategies for targeting p53 as a therapeutic option for cancer.

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Roles of CREB-binding protein (CBP)/p300 in respiratory epithelium tumorigenesis

Cited by 74 publications

References 78 publications

Histone acetylation by CBP and p300 at double-strand break sites facilitates SWI/SNF chromatin remodeling and the recruitment of non-homologous end joining factors

Histone acetylation by CBP and p300 at double-strand break sites facilitates SWI/SNF chromatin remodeling and the recruitment of non-homologous end joining factors

Anacardic acid (6-pentadecylsalicylic acid) induces apoptosis of prostate cancer cells through inhibition of androgen receptor and activation of p53 signaling

Cell fate regulation governed by p53: Friends or reversible foes in cancer therapy

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