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
Introduction SMG1, a phosphatidylinositol 3-kinase-related kinase (PIKK) family serine/threonine kinase, is a key regulator of nonsense-mediated mRNA decay (NMD) through phosphorylation of UPF1 and plays important roles in genome stability, p53 activation, and tumor suppression. Although 77 phosphorylation sites have been reported on SMG1, their regulatory significance has not been systematically characterized. Methods A comprehensive meta-analysis of more than 3,800 PubMed-indexed human phosphoproteomic studies was performed to curate Class I SMG1 phosphosites. A total of 678 qualitative and 173 quantitative phosphoproteomic datasets were analyzed to identify predominant phosphorylation sites. Co-regulation, co-occurrence, motif enrichment, kinase prediction, and cancer phosphoproteomic analyses were conducted to investigate site-specific regulatory networks and biological functions. Results Three C-terminal phosphosites (T3573, S3570, and S3556) emerged as the most frequently detected and dynamically regulated sites across datasets. Co-regulation network analysis indicated distinct functional associations for each site, with T3573 linked to cytoskeletal regulators, S3570 to RNA-processing factors, and S3556 to chromatin- and DNA damage-associated proteins. Co-occurrence analysis suggested that these phosphosites can be phosphorylated simultaneously, indicating coordinated regulation. Multiple core NMD components, including SMG7, UPF1, SMG9, CASC3, and CTIF, exhibited strong positive co-regulation with S3570 and/or S3556. In silico and peptide-array-based kinase predictions identified ATM, PRKDC (DNA-PKcs), and BRAF as candidate upstream kinases for S3556, linking SMG1 phosphorylation to DNA damage signaling. Motif and co-regulation analyses expanded the putative SMG1 substrate repertoire by identifying numerous [S/T]-Q-containing DNA damage response proteins, including BRCA1, RAD51AP1, NBN, PNKP, TP53BP1, and PBRM1. UALCAN analysis further revealed differential regulation of SMG1 phosphosites across multiple cancer types. Discussion These findings identify SMG1 as a central phosphorylation hub integrating nonsense-mediated mRNA decay with genome maintenance pathways and provide the first systematic phosphosite-centric framework for understanding its regulation. The identified regulatory phosphosites, candidate upstream kinases, and phosphorylation networks establish a foundation for future mechanistic studies and support the potential of SMG1 phosphorylation as a diagnostic and therapeutic target in cancer.
Apoorva Pai, Leona Dcunha, Athira Perunelly Gopalakrishnan et al.· Frontiers in Systems Biology· 0 citations
We use cookies to run the site and, with your consent, for analytics and to show ads.
See our Cookie Policy.
