更新于：2024-09-05

PANK4

更新于：2024-09-05

基本信息

别名

4'-phosphopantetheine phosphatase、FLJ10782、hPanK4

+ [3]

简介

Phosphatase which shows a preference for 4'-phosphopantetheine and its oxidatively damaged forms (sulfonate or S-sulfonate), providing strong indirect evidence that the phosphatase activity pre-empts damage in the coenzyme A (CoA) pathway (PubMed:27322068). Hydrolyzing excess 4'-phosphopantetheine could constitute a directed overflow mechanism to prevent its oxidation to the S-sulfonate, sulfonate, or other forms (PubMed:27322068). Hydrolyzing 4'-phosphopantetheine sulfonate or S-sulfonate would forestall their conversion to inactive forms of CoA and acyl carrier protein (PubMed:27322068). May play a role in the physiological regulation of CoA intracellular levels (Probable).

关联

100 项与 PANK4 相关的临床结果

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100 项与 PANK4 相关的转化医学

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0 项与 PANK4 相关的专利（医药）

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146

项与 PANK4 相关的文献（医药）

2024-02-14·Advanced science (Weinheim, Baden-Wurttemberg, Germany)

Kinome-Wide Synthetic Lethal Screen Identifies PANK4 as a Modulator of Temozolomide Resistance in Glioblastoma.

Article

作者: Viviana Vella ; Angeliki Ditsiou ; Anna Chalari ; Murat Eravci ; Sarah K Wooller ; Teresa Gagliano ; Cecilia Bani ; Emanuela Kerschbamer ; Christos Karakostas ; Bin Xu ; Yongchang Zhang ; Frances M G Pearl ; Gianluca Lopez ; Ling Peng ; Justin Stebbing ; Apostolos Klinakis ; Georgios Giamas

Temozolomide (TMZ) represents the cornerstone of therapy for glioblastoma (GBM). However, acquisition of resistance limits its therapeutic potential. The human kinome is an undisputable source of druggable targets, still, current knowledge remains confined to a limited fraction of it, with a multitude of under-investigated proteins yet to be characterized. Here, following a kinome-wide RNAi screen, pantothenate kinase 4 (PANK4) isuncovered as a modulator of TMZ resistance in GBM. Validation of PANK4 across various TMZ-resistant GBM cell models, patient-derived GBM cell lines, tissue samples, as well as in vivo studies, corroborates the potential translational significance of these findings. Moreover, PANK4 expression is induced during TMZ treatment, and its expression is associated with a worse clinical outcome. Furthermore, a Tandem Mass Tag (TMT)-based quantitative proteomic approach, reveals that PANK4 abrogation leads to a significant downregulation of a host of proteins with central roles in cellular detoxification and cellular response to oxidative stress. More specifically, as cells undergo genotoxic stress during TMZ exposure, PANK4 depletion represents a crucial event that can lead to accumulation of intracellular reactive oxygen species (ROS) and subsequent cell death. Collectively, a previously unreported role for PANK4 in mediating therapeutic resistance to TMZ in GBM is unveiled.

2023-12-11·Journal of biomolecular structure & dynamics

In vitro and in silico exploration of newly synthesized triazolyl- isonicotinohydrazides as potent antitubercular agents.

Article

作者: Rajubai D Bakale ; Pramod S Phatak ; Sanket S Rathod ; Prafulla B Choudhari ; Estharla Madhu Rekha ; Dharmarajan Sriram ; Ravibhushan S Kulkarni ; Kishan P Haval

In the present study, we have reported the synthesis of novel isoniazid-triazole derivatives (4a-r), via the click chemistry approach. The synthesized isoniazid-triazole derivatives have potent in vitro antitubercular activity against the Mycobacterium tuberculosis (MTB) H37Rv strain. Among these compounds, 4b, 4f, 4g, 4j, 4k, 4m, 4o, 4p, and 4r were found to be the most active ones with a MIC value of 0.78 μg/mL. This activity is better than ciprofloxacin (MIC value = 1.56 μg/mL) and ethambutol (MIC value = 3.12 μg/mL). The compounds, 4a, 4c, 4d, 4e, 4h, 4i, 4l, and 4n have displayed activity equal to ciprofloxacin (MIC value = 1.56 μg/mL). The cytotoxicity of the active isoniazid-triazole derivatives was studied against RAW 264.7 cell line by MTT assay at 25 μg/mL concentration and no toxicity was observed. Moreover, in-vitro results were supported by in-silico studies with the known antitubercular target (PanK). The drug-likeness, density functional study, molecular docking, and molecular dynamics simulation studies of isoniazid-triazole derivatives validated the ability to form a stable complex with Pantothenate kinase (PanK), which will result in inhibiting the Pantothenate kinase (PanK). Therefore, the results obtained indicate that this class of compounds may offer candidates for future development, and positively provide drug alternatives for tuberculosis treatment.Communicated by Ramaswamy H. Sarma.

2023-12-11·International journal of molecular sciences

Revealing the Mechanisms of Enhanced β-Farnesene Production in Yarrowia lipolytica through Metabolomics Analysis.

Article

作者: Qianxi Liu ; Haoran Bi ; Kai Wang ; Yang Zhang ; Biqiang Chen ; Huili Zhang ; Meng Wang ; Yunming Fang

β-Farnesene is an advanced molecule with promising applications in agriculture, the cosmetics industry, pharmaceuticals, and bioenergy. To supplement the shortcomings of rational design in the development of high-producing β-farnesene strains, a Metabolic Pathway Design-Fermentation Test-Metabolomic Analysis-Target Mining experimental cycle was designed. In this study, by over-adding 20 different amino acids/nucleobases to induce fluctuations in the production of β-farnesene, the changes in intracellular metabolites in the β-farnesene titer-increased group were analyzed using non-targeted metabolomics. Differential metabolites that were detected in each experimental group were selected, and their metabolic pathways were located. Based on these differential metabolites, targeted strain gene editing and culture medium optimization were performed. The overexpression of the coenzyme A synthesis-related gene pantothenate kinase (PanK) and the addition of four mixed water-soluble vitamins in the culture medium increased the β-farnesene titer in the shake flask to 1054.8 mg/L, a 48.5% increase from the initial strain. In the subsequent fed-batch fermentation, the β-farnesene titer further reached 24.6 g/L. This work demonstrates the tremendous application value of metabolomics analysis for the development of industrial recombinant strains and the optimization of fermentation conditions.

项与 PANK4 相关的新闻（医药）

2024-02-15

·Science Daily

New study offers hope for thousands impacted each year by aggressive brain cancer

New research identifies protein (PANK4) as an obstacle that blocks cancer cells from responding to chemotherapeutic treatment for glioblastoma. New research by the University of Sussex could help to increase life expectancy and improve treatment for an aggressive brain cancer, which impacts thousands of people every year in the UK, and hundreds of thousands worldwide. In the study, published in the journal of Advanced Science, researchers have discovered that an understudied protein, called PANK4, is able to block cancer cells from responding to chemotherapeutic treatment for the highly intrusive brain cancer, glioblastoma. Scientists at Sussex have demonstrated that if the protein is removed, cancer cells respond better to the main chemotherapy drug used globally for the treatment of glioblastoma. Prof Georgios Giamas, Professor of Cancer Cell Signalling at the University of Sussex explains: "Glioblastoma is a devastating brain cancer, and researchers are working hard to identify ways to delay progression of the disease, and tackle cell resistance to treatment. As this is the first time that PANK4 has been linked to glioblastoma, the next step is to develop a drug targeting this protein to try to reverse chemo-resistance and restore sensitivity, ensuring that patients receive the best treatment and have better outcomes." Glioblastoma is one of the most aggressive forms of brain cancer. Approximately 3,200 adults are diagnosed with the disease each year in the UK, and around 250,000 -- 300,000 globally, with a best-case survival rate of just one to 18 months after diagnosis. Following surgery to remove the tumour, glioblastoma patients are typically treated with radiation and the chemotherapeutic drug, temozolomide. Although patients initially respond well to the drug, the cancer cells quickly develop resistance to this treatment. The University of Sussex scientists led an international research team to understand the possible reasons for this resistance, helping to guide future therapies to improve quality of life and increase life expectancy for those with glioblastoma. The team identified a protein called PANK4 which, when removed from the cancer cells, can lead to the cell's death, and saw patients better responding to temozolomide. Linked to this, the researchers found that patients expressing high levels of the PANK4 protein had lower survival rates. Dr Viviana Vella, research fellow at the University of Sussex explains: "There are a multitude of under-investigated proteins that may hold great potential for therapeutic intervention. Our study sheds light on this understudied protein, PANK4, unveiling a protective role in temozolomide-resistant cancer cells. Ultimately, PANK4 depletion represents a vulnerability that can now be exploited to restore sensitivity to the drug and improve treatment." This study contributes to a body of ground-breaking research from the Sussex researchers, which focuses on the early diagnosis and treatment of glioblastoma. The research group now hope to develop a drug to reverse chemo-resistance and improve outlook for patients. Ms Charley Cranmer, Director of Fundraising and Communications, Action Against Cancer who funded the research adds: "Action Against Cancer is very proud to have funded this ground-breaking research that offers such hope for patients with this type of aggressive brain cancer."

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