MAPK途径与基因表达的纠缠及其在癌症和神经退行性疾病病因中的普遍存在。

IF 2.6 3区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Biochimica et Biophysica Acta-Gene Regulatory Mechanisms Pub Date : 2023-09-21 DOI:10.1016/j.bbagrm.2023.194988
Joydeep Chakraborty , Sayan Chakraborty , Sohag Chakraborty , Mahesh N. Narayan
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引用次数: 1

摘要

丝裂原活化蛋白激酶(MAPK)是最具特征的细胞信号通路之一,控制包括增殖、分化和凋亡在内的基本细胞过程。这些细胞功能是受MAP激酶信号级联影响和调节的调节基因转录的结果。MAP激酶成分,如受体酪氨酸激酶(RTKs)感知外部线索或配体,并通过多种蛋白质复合物(如RAS-RAF、MEK和ERKs)传递这些信号,最终调节细胞核内的转录因子,以诱导转录和其他调节功能。异常激活、这种信号通路的失调以及这些成分中任何一种的基因改变都会导致发育障碍、癌症和神经退行性疾病。多年来,MAPK通路一直是治疗复杂人类疾病的主要药理靶点,这些疾病与遗传有关,如癌症、阿尔茨海默病、帕金森病和肌萎缩性脊髓侧索硬化症。本文对MAPK通路在基因表达调控中的作用机制进行了综述。此外,从疾病的角度讨论了MAPK成分的机制理解的最新进展。
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Entanglement of MAPK pathways with gene expression and its omnipresence in the etiology for cancer and neurodegenerative disorders

Mitogen Activated Protein Kinase (MAPK) is one of the most well characterized cellular signaling pathways that controls fundamental cellular processes including proliferation, differentiation, and apoptosis. These cellular functions are consequences of transcription of regulatory genes that are influenced and regulated by the MAP-Kinase signaling cascade. MAP kinase components such as Receptor Tyrosine Kinases (RTKs) sense external cues or ligands and transmit these signals via multiple protein complexes such as RAS–RAF, MEK, and ERKs and eventually modulate the transcription factors inside the nucleus to induce transcription and other regulatory functions. Aberrant activation, dysregulation of this signaling pathway, and genetic alterations in any of these components results in the developmental disorders, cancer, and neurodegenerative disorders. Over the years, the MAPK pathway has been a prime pharmacological target, to treat complex human disorders that are genetically linked such as cancer, Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. The current review re-visits the mechanism of MAPK pathways in gene expression regulation. Further, a current update on the progress of the mechanistic understanding of MAPK components is discussed from a disease perspective.

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来源期刊
CiteScore
9.20
自引率
2.10%
发文量
63
审稿时长
44 days
期刊介绍: BBA Gene Regulatory Mechanisms includes reports that describe novel insights into mechanisms of transcriptional, post-transcriptional and translational gene regulation. Special emphasis is placed on papers that identify epigenetic mechanisms of gene regulation, including chromatin, modification, and remodeling. This section also encompasses mechanistic studies of regulatory proteins and protein complexes; regulatory or mechanistic aspects of RNA processing; regulation of expression by small RNAs; genomic analysis of gene expression patterns; and modeling of gene regulatory pathways. Papers describing gene promoters, enhancers, silencers or other regulatory DNA regions must incorporate significant functions studies.
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