Mechanistically, ZNF207 contributes to tumour development and progression through modulation of major oncogenic signalling pathways, including phosphoinositide 3-kinase/protein kinase B/mechanistic target of rapamycin signalling, nuclear factor erythroid 2-related factor 2 (NRF2)-related ferroptosis, spindle checkpoint and immune-regulatory pathways.
Abstract
Zinc finger protein 207 (ZNF207), a member of the Cys2His2 (C2H2)-type zinc finger protein family, functions as a transcriptional regulator involved in key cellular processes, including proliferation, differentiation, and tumourigenesis. Through its zinc finger motifs, microtubule-binding region, GLEBS motif, intrinsically disordered region, and nuclear localization signal, ZNF207 participates in mitotic regulation, pluripotency maintenance, RNA processing, and context-dependent transcriptional control. Aberrant ZNF207 expression has been associated with disease progression and adverse clinical outcomes in several cancer types, although the strength of evidence varies across disease contexts. Mechanistically, ZNF207 contributes to tumour development and progression through modulation of major oncogenic signalling pathways, including phosphoinositide 3-kinase/protein kinase B/mechanistic target of rapamycin (PI3K/AKT/mTOR) signalling, nuclear factor erythroid 2-related factor 2 (NRF2)-related ferroptosis, spindle checkpoint and immune-regulatory pathways. Given its multifaceted regulatory roles in cancer biology, ZNF207 has emerged as a promising target for precision oncology. Further elucidation of its molecular mechanisms may facilitate the development of early diagnostic strategies and targeted therapeutic interventions.
The mesenchymal homeobox transcription factor MEOX2 is recognized for its roles in development and homeostasis, but the full landscape of its complex and often contradictory functions in human diseases, along with its potential unifying regulatory logic, remains to be systematically elucidated. This Review synthesizes current evidence to provide a comprehensive overview of MEOX2’s widespread roles in both neoplastic and non-neoplastic diseases. MEOX2 is remarkably context-dependent: it acts as an oncogene in glioblastoma and lung cancer, but as a tumour suppressor in breast cancer, hepatocellular carcinoma and other tumour types. Its dysregulation is also linked to neurovascular deficits in Alzheimer disease (AD), cardiovascular disorders, metabolic fibrosis and developmental malformations. This functional versatility stems from MEOX2’s role as a key signalling integrator, subject to fine-tuned regulation by epigenetic mechanisms, non-coding RNA networks and core pathways including PI3K/AKT, ERK and Hedgehog (Hh). Given the strong association between MEOX2 expression and clinical outcomes, it has emerged as a potential diagnostic and prognostic biomarker for several diseases. Intervention strategies targeting MEOX2 and its regulatory networks show translational promise. This Review proposes a conceptual framework placing MEOX2 as a ‘cross-disease core regulatory node’, systematically delineates its complex disease associations and molecular mechanisms, and charts a course for the future development of precision medicine strategies targeting MEOX2.
Yi Liu, Minming Yi, Chunrong Tang et al.· Frontiers in Cell and Develo...· 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
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
An integrated overview of the molecular features and functional roles of BAP1 is provided, with particular emphasis on its impacts on the regulation of cell death including apoptosis, ferroptosis and disulfidptosis.
Kexin Fan, Jun Yao, Shaobo Wu et al.· Frontiers in Cell and Develo...· 0 citations
Plant Homeodomain Finger Protein 14 (PHF14) is a known epigenetic regulator involved in chromatin-mediated gene regulation. PHF14 belongs to the plant homeodomain (PHD) family, and possesses four PHD zinc-finger domains. The N-terminal PHD1 and PHD2 domain of PHF14 mediate histone recognition through specific PHD1–ZnK–PHD2 (PZP) cassettes and thereby contribute to the regulation of transcriptional activation and gene silencing. PHF14 plays a role in regulating essential cellular processes such as the cell cycle, mesenchymal proliferation, DNA damage response, and B-cell proliferation. Genetic variants of PHF14 have been identified across multiple clinical conditions, underscoring its physiological and pathologic relevance. Over the past 5 years, PHF14 has garnered substantial attention for its dysregulation or sequence variation associated with various cancers. PHF14-mediated interactions are implicated in neurodevelopmental disorders and also contribute to lung and renal fibrosis, as well as Dandy–Walker syndrome, underscoring its role in diverse pathological conditions. This review summarizes current knowledge on PHF14 structure, interaction partners, molecular functions, associated signaling pathways, and roles in diseases.
Vaishnavi Gopalakrishnan, Amal Fahma, Rajesh Raju et al.· Frontiers in Molecular Biosc...· 0 citations
The ubiquitin-proteasome system maintains cellular protein turnover and quality control through the coordinated action of ubiquitin ligases and deubiquitinating enzymes (DUBs). While the functions of E3 ubiquitin ligases have been extensively investigated in renal disease, the ~100 human DUBs distributed across seven structurally distinct families have recently emerged as important regulators of renal physiology and pathology. The present review organizes current knowledge of DUB-mediated regulation in kidney disease around functional themes rather than individual disease categories. The present review discusses how DUBs regulate inflammatory signaling, TGF-β-mediated fibrotic responses, epithelial-to-mesenchymal transition (EMT), mitochondrial homeostasis, multiple forms of programmed cell death, podocyte homeostasis, and oncogenic pathways in renal cell carcinoma. Several DUBs, including A20 (TNFAIP3), CYLD, USP25 and OTUD5, restrain inflammation and fibrosis, whereas USP11, OTUD1, and USP22 promote disease progression through substrate stabilization. The translational landscape of DUB inhibitors, PROTAC degraders, and the DUBTAC platform for targeted protein stabilization, along with the selectivity and delivery challenges that remain, were discussed. Key unanswered questions, including cell-type-specific DUB functions, ubiquitin chain linkage context, and the therapeutic window for DUB modulation in the kidney, are outlined as priorities for future investigation.
Qianqian Li, Yufang Ni, Zhaoyang Li et al.· Molecular Medicine Reports· 0 citations
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