EP300

What is ep300 protein?

EP300 protein, also known as histone acetyltransferase p300, is a transcriptional coactivator that functions in chromatin remodeling and regulation of gene expression. EP300 belongs to the p300/CBP family of proteins. It has histone acetyltransferase (HAT) activity.As a HAT, it acetylates histones and other proteins, thereby regulating gene transcription. It adds acetyl groups to lysine residues on histone tails.This acetylation neutralizes the positive charge on histones and leads to an opened chromatin state, making DNA more accessible for transcription.

EP300 interacts with various transcription factors like p53, STAT3, HIF1-α, NF-κB, Smad7 etc and regulates their target genes. It plays a key role in cell proliferation, differentiation and apoptosis. EP300 is involved in many cellular processes like DNA damage response, cell cycle progression, DNA repair, cellular senescence and cancer development.Mutations and deletions in EP300 have been linked to Rubinstein-Taybi syndrome and various cancers like liver cancer and leukemia.It acts as a transcriptional co-activator for CREB and p53 and regulates key genes involved in cell survival, proliferation and apoptosis.

What is the function of ep300 protein?

Histone acetyltransferase (HAT) activity: EP300 has intrinsic HAT activity. It acetylates lysine residues on histone tails, especially H3K18 and H3K27. This acetylation neutralizes positive charge on histones and results in relaxed chromatin confirmation. This opens up chromatin structure and makes DNA accessible for transcription.

Transcriptional co-activator function: EP300 interacts with various transcription factors like p53, HIF1-α, NF-κB etc. It acts as a bridging factor between DNA-binding transcription factors and basal transcription machinery. This enhances transcription of target genes of these transcription factors.

Regulation of key cellular processes: EP300 regulates genes involved in cell cycle, apoptosis, DNA damage response etc. It is required for p53-dependent transcriptional activation and apoptosis in response to stress. Also involved in processes like cellular senescence, differentiation, DNA repair and cancer development.

Ep300 related signaling pathway

p53 signaling pathway: EP300 directly interacts with and acetylates p53 in response to various stresses. This acetylation enhances p53 stability, DNA binding and transcriptional activity. EP300 co-activates transcription of p53 target genes involved in cell cycle arrest, apoptosis and senescence.

Hypoxia signaling pathway: EP300 interacts with and acetylates hypoxia inducible factor 1α (HIF1α). This acetylation stabilizes HIF1α under hypoxic conditions and enhances its transcriptional activity. Induces transcription of genes regulating angiogenesis, metabolism, cell survival during hypoxia.

Wnt/β-catenin signaling pathway: EP300 interacts with nuclear β-catenin and mediates its transcriptional co-activator function. Regulates Wnt target genes involved in proliferation, development, stem cell self-renewal and cancer.

NF-κB signaling pathway: Binds to NF-κB and enhances transcription of inflammation-related genes. Regulates immune response, inflammation, apoptosis, cell survival and proliferation.

Ep300 Related Diseases

•  Rubinstein-Taybi Syndrome: A genetic developmental disorder caused by mutations in EP300 or CBP genes. Features include broad thumbs/halluces and facial abnormalities.
•  Cancers: Reduced EP300 expression in many cancers like liver, breast, colon cancers correlates with poor prognosis. It acts as a tumor suppressor.
•  Lung cancer: EP300 mutations or reduced expression promote metastasis, epithelial-mesenchymal transition and stemness in lung cancers.
•  Drug target for cancers: Inhibiting EP300 HAT activity can suppress tumor growth by modulating key oncogenic signaling pathways. EP300 inhibitors are in preclinical/clinical trials.
•  Biomarker for cancer prognosis: EP300 levels can serve as biomarker for predicting cancer metastasis and survival outcomes to enable personalized medicine.

Biomedical Application of ep300 Protein

•  Drug target for cancers: Inhibiting EP300 HAT activity can suppress tumor growth by modulating key oncogenic signaling pathways. EP300 inhibitors are in preclinical/clinical trials.
•  Therapeutic approach for Rubinstein-Taybi syndrome: Gene therapy using vectors to restore EP300 expression may help treat developmental defects in RTS patients.
•  Dissecting p53 tumor suppression pathway: EP300 knockout and rescue models help elucidate precise mechanisms of p53 acetylation and target gene regulation in cancer.

•  Dissecting p53 tumor suppression pathway: EP300 knockout and rescue models help elucidate precise mechanisms of p53 acetylation and target gene regulation in cancer.