Jul 2026· Frontiers in Cell and Developmental Biology· Vol 14· 0 citations· 101 references
Medicine
TL;DR
This review establishes a comprehensive theoretical framework for understanding the role of ATP5A1 in disease pathogenesis and supports its potential utility in precision diagnostics and therapeutics.
Abstract
ATP5A1 acts as a crucial gene that encodes the core α subunit of the mitochondrial F1-ATPase complex to regulate cellular oxidative phosphorylation (OXPHOS) and maintain energy homeostasis. Consequently, its dysregulation—whether through aberrant expression, genomic alterations, or aberrant post-translational modifications—is hypothesized to be a key potential molecular event contributing to the pathogenesis of malignant tumors, neurodegenerative lesions, and metabolic dysregulation.This review systematically summarizes the molecular structure, biological functions, and regulatory networks of ATP5A1. A comprehensive overview of its expression patterns and pathogenic mechanisms across various diseases, including lung, colorectal, liver, and gastric cancers, as well as non-neoplastic conditions, is provided. Besides, emphasis is placed on the clinical translational potential of ATP5A1 as a diagnostic biomarker and therapeutic target, with recent advances in this area critically evaluated. Furthermore, current challenges and limitations in ATP5A1-related research are discussed, and future directions are proposed to facilitate mechanistic investigations and clinical applications. Collectively, this review establishes a comprehensive theoretical framework for understanding the role of ATP5A1 in disease pathogenesis and supports its potential utility in precision diagnostics and therapeutics.
Protein phosphatase 2A (PP2A) is a highly conserved serine/threonine phosphatase that plays a pivotal role in maintaining cellular homeostasis by counterbalancing kinase activity. As a heterotrimeric enzyme composed of scaffolding, regulatory, and catalytic subunits, PP2A achieves extraordinary functional diversity through the dynamic assembly of more than 80 holoenzyme variants. This structural versatility allows PP2A to regulate a wide range of biological processes, including cell cycle progression, apoptosis, DNA damage response, and major signaling pathways such as MAPK and Wnt. Dysregulation of PP2A, through altered subunit expression, post-translational modification, or inhibition by endogenous suppressors like CIP2A and SET, has been implicated in diverse diseases, notably neurodegenerative disorders, cancers, and metabolic syndromes. In neurological disorders such as Alzheimer's and Parkinson's diseases, impaired PP2A activity contributes to pathogenic protein hyperphosphorylation, neurofibrillary tangle formation, and neuroinflammation. Recent advances have fundamentally reshaped our understanding of PP2A biology. High-resolution structural studies have revealed the molecular basis of holoenzyme assembly and substrate recruitment, while accumulating evidence suggests that PP2A activity is dynamically regulated across tissues and cell types, largely driven by differential expression of regulatory subunits and post-translational modifications. Despite these advances, current knowledge remains fragmented, and a comprehensive synthesis linking PP2A structural dynamics, regulatory mechanisms, and its roles in pathophysiology, particularly in the context of neurological disorders, is still lacking. This review deciphers the structural complexity and regulatory mechanisms of PP2A, elucidates its multifaceted roles in neural physiology and pathology, and examines current and emerging therapeutic strategies targeting PP2A modulation to intervene in neurological disease.
Jingyi Tian, Rui Yao, Lu Shen et al.· Current Neuropharmacology· 0 citations
OTUD1 is a deubiquitinase of the OTU family that participates in immune signaling, redox balance, and cell death through modulating substrate ubiquitination. Under physiological conditions, OTUD1 primarily exerts negative regulatory effects, restricting excessive activation of NF-κB inflammatory signaling and type I interferon responses, thereby maintaining immune and oxidative homeostasis. Under pathological conditions, its functional effects undergo tissue-dependent reprogramming: it is downregulated in most epithelial tumors and suppresses malignant progression, whereas it is upregulated in certain tumors and cardiovascular or metabolic diseases and promotes pathological remodeling. It exerts protective regulation in the nervous system and mucosal inflammation, yet drives hypertrophy and fibrosis in the cardiovascular system. Preclinical studies indicate that OTUD1 expression levels correlate with tumor stage, prognosis, and therapeutic sensitivity, suggesting potential as a biomarker for diagnostic subtyping and prognostic assessment. However, marked tissue functional heterogeneity, the discovery of non-enzymatic scaffold functions, and the lack of highly selective targeting probes constitute central bottlenecks for clinical translation. This review systematically summarizes the molecular characteristics, physiological functions, disease regulatory networks, and current clinical translational status of OTUD1, with the aim of clarifying the molecular basis of its functional duality and providing a theoretical foundation for optimizing precision diagnostic and therapeutic strategies targeting OTUD1.
Qing-Song Wang, Lijuan Zhang, Hong-Mei Cao et al.· Frontiers in Immunology· 0 citations
Emerging evidence has expanded the functional repertoire of SKP2 beyond cell cycle control to encompass metabolism, DNA repair, stemness, tumor microenvironment and immunotherapy response, positioning it as an increasingly attractive target for intervention.
Sheng-An Zheng, Cheng Wang, Xiao-Die Yao et al.· Drug Design, Development and...· 0 citations
DExH-box helicase 9 (DHX9) is a multifunctional nucleic acid helicase that participates in R-loop homeostasis, genome maintenance, RNA metabolism, and innate immune signaling. Accumulating evidence has linked aberrant DHX9 expression or activity to tumorigenesis, tumor progression, treatment response, and patient prognosis. However, its role in cancer is highly context-dependent, rather than uniformly oncogenic or tumor suppressive. Depending on its molecular partners, subcellular localization, post-translational modifications, tumor genotype, and immune microenvironment, DHX9 may either promote malignant phenotypes or contribute to tumor-restraining processes. In this review, we summarize the molecular characteristics and regulatory properties of DHX9, discuss its roles in genome stability, transcriptional and post-transcriptional control, circular RNA (circRNA) biogenesis, and tumor-immune crosstalk, and evaluate its emerging value as a potential biomarker and therapeutic target. We also highlight key challenges in this field, including mechanistic heterogeneity, insufficient translational validation, and the urgent need for context-informed patient stratification to maximize the clinical utility of DHX9-targeted strategies.
Yejin Cai, Ziyuan Chen, Jiaying Xiong et al.· Biochimica et biophysica act...· 0 citations
Cancer is among the leading causes of death worldwide, and its development has been a consistent focus of research. Many investigations have demonstrated the close relationship between epigenetic mechanisms and cancer development. Posttranslational modifications (PTMs) are pivotal regulators of cancer biology, orchestrating protein functional diversity, epigenetic reprogramming, and metabolic adaptation to drive tumor initiation and progression.In addition to classical phosphorylation and acetylation, advancements in mass spectrometry have led to the discovery of more forms of protein modification. These modifications bridge metabolic dysregulation and oncogenic reprogramming. In this review, we summarize current knowledge on the molecular mechanisms underlying nine novel acylations in cancer, including the roles of acyltransferases, deacylases, and metabolic enzymes in generating acyl-CoA donors. We highlight preclinical and clinical evidence linking aberrant acylation to cancer progression, with a focus on emerging therapeutic strategies targeting acylation enzymes and their combination with immunotherapy or metabolic interventions. Key research gaps are identified, including the need for high-resolution profiling of acylation dynamics, tissue-specific biomarkers, and mechanistic studies on rare types of acylation. By integrating basic research and translational insights, this review highlights the translational potential of novel types of acylation as both a prognostic marker and a therapeutic target in precision oncology.
Heng-Hui Yang, Jia-Mi Huang, Yueyou Wang et al.· Critical reviews in oncology...· 0 citations
PRMT8 encodes a protein arginine methyltransferase, which is primarily expressed in the brain and nervous system. Several studies have reported its alterations, which have been implicated in various cancers. However, the existing information remains unsystematic and fragmented due to inconsistency in methodology. This review aims to explore PRMT8 gene alterations in humans, their effects on cellular function and physiology, and their clinical implications. We conducted a narrative literature review covering all publications on PRMT8 alterations across different cancer types, their effect on tumour cell characteristics, and their impact on patient prognosis. Reported PRMT8 alterations include mutations, copy number amplifications, and single-nucleotide polymorphisms, which lead to overexpression or downregulation of PRMT8 protein in tumour cells. PRMT8 alterations compromise the efficacy of both chemotherapy and immune checkpoint inhibitor treatment. These alterations enable tumour cells to maintain pluripotency via activation of the PI3K/AKT/SOX2 signalling pathway, thereby promoting cellular proliferation, invasion, and colony formation. Clinically, these PRMT8 alterations drive disease progression and therapy resistance, resulting in poor prognosis and reduced patient survival. These findings underscore the need to incorporate PRMT8 alterations assessment in clinical practice to guide therapeutic decision-making and improve treatment outcomes in affected patient populations.
Choo-Yuen Ting, Sheron Goh Sir Loon, L. Sun et al.· Critical reviews in oncology...· 0 citations
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