Activation of RASSF2A by p300 induces late apoptosis through histone hyperacetylation

Liu, Chungang; Pan, Yunhui; Wang, Xiuli; Lü, Jun; Huang, Baiqu; Li, Xiaoxue

doi:10.1042/cbi20090388

Cited by 7 publications

(6 citation statements)

References 28 publications

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“…EP300, as well as GLRXP3 and CNTD2, has also been shown to be related to the NF-B transcriptional response, regulating cell survival and innate immune responses (16). At least six genes, ETS1, GLRXP3, EP300, GCGR, SEC61g, and ZNF205, are associated with cell death/apoptosis (17)(18)(19).…”

Section: Primary Rnai Screen In Hep-2c Cellsmentioning

confidence: 99%

Engineering Enhanced Vaccine Cell Lines To Eradicate Vaccine-Preventable Diseases: the Polio End Game

Sanden

Wang

Dybdahl‐Sissoko

et al. 2016

J Virol

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Vaccine manufacturing costs prevent a significant portion of the world's population from accessing protection from vaccinepreventable diseases. To enhance vaccine production at reduced costs, a genome-wide RNA interference (RNAi) screen was performed to identify gene knockdown events that enhanced poliovirus replication. Primary screen hits were validated in a Vero vaccine manufacturing cell line using attenuated and wild-type poliovirus strains. Multiple single and dual gene silencing events increased poliovirus titers >20-fold and >50-fold, respectively. Host gene knockdown events did not affect virus antigenicity, and clustered regularly interspaced short palindromic repeat (CRISPR)-Cas9-mediated knockout of the top candidates dramatically improved viral vaccine strain production. Interestingly, silencing of several genes that enhanced poliovirus replication also enhanced replication of enterovirus 71, a clinically relevant virus to which vaccines are being targeted. The discovery that host gene modulation can markedly increase virus vaccine production dramatically alters mammalian cell-based vaccine manufacturing possibilities and should facilitate polio eradication using the inactivated poliovirus vaccine. IMPORTANCEUsing a genome-wide RNAi screen, a collection of host virus resistance genes was identified that, upon silencing, increased poliovirus and enterovirus 71 production by from 10-fold to >50-fold in a Vero vaccine manufacturing cell line. This report provides novel insights into enterovirus-host interactions and describes an approach to developing the next generation of vaccine manufacturing through engineered vaccine cell lines. The results show that specific gene silencing and knockout events can enhance viral titers of both attenuated (Sabin strain) and wild-type polioviruses, a finding that should greatly facilitate global implementation of inactivated polio vaccine as well as further reduce costs for live-attenuated oral polio vaccines. This work describes a platform-enabling technology applicable to most vaccine-preventable diseases. Vaccines are important defenses in the fight against infectious disease. Currently, a complex set of factors such as population dynamics and bioproduction costs limit the ability to provide adequate immunization coverage to many economically distressed countries. The current efforts to eradicate poliovirus exemplify these challenges. The oral polio vaccine (OPV), consisting of attenuated Sabin strains, has reduced the total number of poliomyelitis cases by Ͼ99% since the late 1980s. However, live attenuated strains carry the risk of phenotypic reversion to a neurovirulent "vaccine-derived poliovirus" (VDPV) capable of inducing vaccine-associated paralytic poliomyelitis (VAPP) (1, 2). To prevent the emergence and circulation of VDPVs during the polio eradication effort and beyond, OPV must be replaced by the inactivated poliovirus vaccine (IPV) (3). The cost of IPV, which is approximately $3.00 per dose compared to approximately $0.20 for OPV, is a major o...

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Section: Primary Rnai Screen In Hep-2c Cellsmentioning

confidence: 99%

Engineering Enhanced Vaccine Cell Lines To Eradicate Vaccine-Preventable Diseases: the Polio End Game

Sanden

Wang

Dybdahl‐Sissoko

et al. 2016

J Virol

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“…Members of this family have been reported to suppress cell growth when expressed exogenously in cultured cells (11). The RASSF2 gene has been shown to be frequently inactivated by promoter methylation in a wide range of tumor types, including colorectal, gastric, oral, nasopharyngeal, breast and lung cancers (12)(13)(14)(15)(16).…”

Section: Introductionmentioning

confidence: 99%

Ectopic expression of RASSF2 and its prognostic role for gastric adenocarcinoma patients

Luo

et al. 2011

Experimental and Therapeutic Medicine

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Abstract. RASSF2 has recently been identified as a potential tumor suppressor that serves as a Ras effector in various types of human cancers. However, there have been few reports detailing this in gastric cancer. Samples of gastric adenocarcinoma from 276 Chinese patients with follow-up were analyzed for RASSF2 protein expression by immunohistochemistry. RASSF2 was expressed in up to 31.2% (86/276) of this group of gastric carcinoma. The expression of RASSF2 was significantly lower in carcinomas than in normal mucosas (P<0.05). RASSF2 corresponded positively with patient age, histological differentiation, depth of tumor invasion, regional lymph node and distant metastasis, and TNM stage (all P<0.05). Further multivariate analysis revealed that patient gender, depth of tumor invasion, distant metastasis, TNM stage and the expression of RASSF2 were independent prognostic factors for patients with gastric cancer. The Kaplan-Meier plot showed that the overall mean survival time of the patients with RASSF2-negative expression was shorter than that of patients with positive expression (χ 2 =156.874, P<0.0001). Moreover, RASSF2-negative expression had a much more significant effect on the survival of those patients with early stage tumors (χ 2 =127.167, P<0.0001), highlighted by a >50.9% reduction in 3-year survival compared to that of patients with RASSF2-positive expression. In late stages, the difference was also significant (χ 2 =6.246, P= 0.019), with a 35.5% reduction in 3-year survival. It is suggested that RASSF2 plays an important role in the evolution of gastric adenocarcinoma and should be considered as a potential marker for its prognosis.

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“…p300 can function as an acetyltransferase to modify certain proteins and then participate in the transcription process. For instance, in gastric cancer and melanoma, p300 affects the proliferation, cell cycle and ageing of tumour cells to some extent by acetylating histones to promote transcription of the corresponding genes [ 59 , 60 ], and a similar finding was found in diffuse large B-cell lymphoma (DLBCL) [ 61 ]. p300 also regulates transcriptional processes in prostate cancer; on the one hand, p300 recognise phosphorylated AR, which promotes subsequent AR acetylation at K609, thereby facilitating transcription [ 62 ].…”

Section: P300 and Tumoursmentioning

confidence: 99%

“…Ono et al performed pancreatic cancer cell-related experiments and found that the expression of apoptosis-related proteins such as cleaved caspases 3, 8, and 9 and PARP was increased after p300 interference, and acetylation of H3K27 was also inhibited by C646 treatment, suggesting that p300 may regulate apoptosis of pancreatic cancer cells via its HAT activity [ 83 ]. Liu et al found that p300 is involved in the acetylation of H3 and H4 on the RASSF2A promoter and regulates RASSF2A expression, which in turn induces the apoptosis of gastric cancer cells [ 59 ]. In studies by Fu and others, C646 treatment led to the apoptosis of AML1-ETO-positive AML cell lines and primary parental cells, while normal haematopoietic stem cells were not affected [ 100 , 112 ].…”

Section: P300 and Tumoursmentioning

confidence: 99%

Effects of the Acetyltransferase p300 on Tumour Regulation from the Novel Perspective of Posttranslational Protein Modification

et al. 2023

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p300 acts as a transcription coactivator and an acetyltransferase that plays an important role in tumourigenesis and progression. In previous studies, it has been confirmed that p300 is an important regulator in regulating the evolution of malignant tumours and it also has extensive functions. From the perspective of non-posttranslational modification, it has been proven that p300 can participate in regulating many pathophysiological processes, such as activating oncogene transcription, promoting tumour cell growth, inducing apoptosis, regulating immune function and affecting embryo development. In recent years, p300 has been found to act as an acetyltransferase that catalyses a variety of protein modification types, such as acetylation, propanylation, butyylation, 2-hydroxyisobutyration, and lactylation. Under the catalysis of this acetyltransferase, it plays its crucial tumourigenic driving role in many malignant tumours. Therefore, the function of p300 acetyltransferase has gradually become a research hotspot. From a posttranslational modification perspective, p300 is involved in the activation of multiple transcription factors and additional processes that promote malignant biological behaviours, such as tumour cell proliferation, migration, and invasion, as well as tumour cell apoptosis, drug resistance, and metabolism. Inhibitors of p300 have been developed and are expected to become novel anticancer drugs for several malignancies. We review the characteristics of the p300 protein and its functional role in tumour from the posttranslational modification perspective, as well as the current status of p300-related inhibitor research, with a view to gaining a comprehensive understanding of p300.

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Activation of RASSF2A by p300 induces late apoptosis through histone hyperacetylation

Cited by 7 publications

References 28 publications

Engineering Enhanced Vaccine Cell Lines To Eradicate Vaccine-Preventable Diseases: the Polio End Game

Engineering Enhanced Vaccine Cell Lines To Eradicate Vaccine-Preventable Diseases: the Polio End Game

Ectopic expression of RASSF2 and its prognostic role for gastric adenocarcinoma patients

Effects of the Acetyltransferase p300 on Tumour Regulation from the Novel Perspective of Posttranslational Protein Modification

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