Conserved RNA Binding Activity of Phosphatidyl Inositol 5-Phosphate 4-Kinase (PIP4K2A)

Behari, Jatin; Borkar, Pranita; Vindu, Arya; Dandewad, Vishal; Upadrasta, Sindhuri; Shanmugam, Dhanasekaran; Seshadri, Vasudevan

doi:10.3389/fmolb.2021.631281

Cited by 3 publications

(2 citation statements)

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“…The absence of nuclear localization indicates that transcription of certain genes may be affected. Additionally, a recent study reported that RNA‐binding activity enables the PIP4K2A protein to regulate protein synthesis at the translational level 18 . Overall, our results suggest that alteration of subcellular localization and phosphorylation status for the S316R mutant may have regulatory effects on expression of β‐globin in multiple ways; studies are ongoing to explore the detailed mechanism.…”

Section: Resultsmentioning

confidence: 52%

“…Additionally, a recent study reported that RNA-binding activity enables the PIP4K2A protein to regulate protein synthesis at the translational level. 18 Overall, our results suggest that alteration of subcellular localization and phosphorylation status for the S316R mutant may have regulatory effects on expression of β-globin in multiple ways; studies are ongoing to explore the detailed mechanism. In addition, the innovative treatments towards thalassemia are being developed continuously.…”

Section: R E Su Lts a N D Discussionmentioning

confidence: 71%

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A novel gain‐of‐function PIP4K2A mutation elevates the expression of β‐globin and aggravates the severity of α‐thalassemia

et al. 2023

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SummaryHaemoglobin H (Hb H) disease (intermediate status of α‐thalassemia) shows marked phenotypic variability from asymptomatic to severe anaemia. Apart from the combined β‐thalassemia allele ameliorating clinical severity, reports of genetic modifier genes affecting the phenotype of Hb H disease are scarce which bring inconvenience to precise diagnosis and genetic counselling of the patients. Here, we present a novel mutation (c.948C>A, p.S316R) in the PIP4K2A gene in a female Hb H disease patient who displayed moderate anaemia and a relatively high Hb H level. Haematological analysis in her family members revealed that individuals carrying this mutation have upregulated β‐globin expression, leading to a more imbalanced β/α‐globin ratio and more Hb H inclusion bodies in peripheral red blood cells. According to functional experiments, the mutant PIP4K2A protein exhibits enhanced protein stability, increased kinase activity and a stronger regulatory effect on downstream proteins, suggesting a gain‐of‐function mutation. Moreover, introduction of the S316R mutation into HUDEP‐2 cells increased expression of β‐globin, further inhibiting erythroid differentiation and terminal enucleation. Thus, the S316R mutation is a novel genetic factor associated with β‐globin expression, and the PIP4K2A gene is a new potential modifier gene affecting the α‐thalassemia phenotype.

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Section: Resultsmentioning

confidence: 52%

Section: R E Su Lts a N D Discussionmentioning

confidence: 71%

A novel gain‐of‐function PIP4K2A mutation elevates the expression of β‐globin and aggravates the severity of α‐thalassemia

et al. 2023

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Exploring new mechanisms in cancer molecular pathways and pathogenic cell transformation: PIP4K2A as a prognostic marker and therapeutic target in cutaneous malignant melanoma

Luo,

Song,

Shen

et al. 2024

Discov Onc

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Background Cutaneous malignant melanoma is a very aggressive and metastatic form of skin cancer, typically linked with poor outcomes. Advances in genomic analysis have underscored the crucial role of T cells in tumor immunity. Immune checkpoint inhibitors have notably transformed melanoma treatment by boosting T cell activity. Studies of gene expression have found that the phosphatidylinositol-4-phosphate kinase 2A (PIP4K2A) gene is abnormally expressed in various tumors, indicating its potential role in tumor progression. Utilizing single-cell sequencing and machine learning, researchers can now explore the complex interactions between T cells and melanoma cells at a genomic level. This study aimed to investigate the role of the PIP4K2A gene in cutaneous malignant melanoma, with a focus on its influence on T cell-mediated immune responses. Methods Samples from cutaneous melanoma patients were analysed by single-cell transcriptome for differentially expressed genes and signalling pathways associated with cutaneous melanoma. Then, genes were identified and predictive models were built based on the transcriptomic data using machine learning models to assess whether the expression level of PIP4K2A could effectively predict the malignancy and prognosis of cutaneous melanoma. In addition, we also performed drug therapy predictive analysis and immunotherapy analysis.Finally, the critical role of PIP4K2A in cutaneous melanoma was further confirmed by immunohistochemistry. Results The PIP4K2A gene exhibited a significantly elevated expression level in cutaneous malignant melanoma, showing a strong correlation with the clinical stage and patient prognosis. At the therapeutic level, high PIP4K2A expression is less responsive to immunotherapy, and this gene is a risk factor for drug therapy in cutaneous malignant melanoma. Additionally, our experimental outcomes validated this observation. Conclusions The PIP4K2A gene could be a crucial prognostic marker for cutaneous malignant melanoma, as it significantly affects T cell activity within the tumor microenvironment. This study offers essential insights into melanoma pathogenesis and assists in pinpointing new early diagnostic markers and therapeutic targets. Utilizing advanced genomic tools and computational techniques, the research enhances our understanding of T cell dynamics in melanoma, facilitating the development of personalized medicine and more effective immunotherapy strategies. Supplementary Information The online version contains supplementary material available at 10.1007/s12672-024-01555-3.

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PIP kinases: A versatile family that demands further therapeutic attention

Llorente¹,

Arora²,

Grenier³

et al. 2023

Advances in Biological Regulation

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Conserved RNA Binding Activity of Phosphatidyl Inositol 5-Phosphate 4-Kinase (PIP4K2A)

Cited by 3 publications

References 36 publications

A novel gain‐of‐function PIP4K2A mutation elevates the expression of β‐globin and aggravates the severity of α‐thalassemia

A novel gain‐of‐function PIP4K2A mutation elevates the expression of β‐globin and aggravates the severity of α‐thalassemia

Exploring new mechanisms in cancer molecular pathways and pathogenic cell transformation: PIP4K2A as a prognostic marker and therapeutic target in cutaneous malignant melanoma

PIP kinases: A versatile family that demands further therapeutic attention

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