Autor: |
Zhu, Yu, Wang, Zi, Li, Yanan, Peng, Hongling, Liu, Jing, Zhang, Ji, Xiao, Xiaojuan |
Předmět: |
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Zdroj: |
Cancers; Feb2023, Vol. 15 Issue 4, p1219, 24p |
Abstrakt: |
Simple Summary: Through their regulatory effects on gene expression, histone acetyltransferases have been implicated in the normal physiological activities and genesis of cancer. Genetic aberrations of CREBBP/EP300 have been observed in various types of solid tumors and hematologic malignancies, making them serve as promising therapeutic targets. Here, this review discusses the critical role of CREBBP/EP300 in normal hematopoiesis and also provides a comprehensive overview of how they contribute to the genesis and progression of hematologic malignancies. The impact of different CREBBP/EP300 inhibitors and histone deacetylase inhibitors on targeting therapeutic potential, alleviating chemotherapy resistance, and enhancing immunotherapeutic potential has also been reviewed. Disordered histone acetylation has emerged as a key mechanism in promoting hematological malignancies. CREB-binding protein (CREBBP) and E1A-binding protein P300 (EP300) are two key acetyltransferases and transcriptional cofactors that regulate gene expression by regulating the acetylation levels of histone proteins and non-histone proteins. CREBBP/EP300 dysregulation and CREBBP/EP300-containing complexes are critical for the initiation, progression, and chemoresistance of hematological malignancies. CREBBP/EP300 also participate in tumor immune responses by regulating the differentiation and function of multiple immune cells. Currently, CREBBP/EP300 are attractive targets for drug development and are increasingly used as favorable tools in preclinical studies of hematological malignancies. In this review, we summarize the role of CREBBP/EP300 in normal hematopoiesis and highlight the pathogenic mechanisms of CREBBP/EP300 in hematological malignancies. Moreover, the research basis and potential future therapeutic implications of related inhibitors were also discussed from several aspects. This review represents an in-depth insight into the physiological and pathological significance of CREBBP/EP300 in hematology. [ABSTRACT FROM AUTHOR] |
Databáze: |
Complementary Index |
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