Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Phosphatidylinositol (PI) lipids have a predominance of a single molecular species present through the organism. In healthy mammals this molecular species is 1-stearoyl-2-arachidonoyl (18:0/20:4) PI. Although the importance of PI lipids for cell physiology has long been appreciated, less is known about the biological role of enriching PI lipids with 18:0/20:4 acyl chains. In conditions with dysfunctional lipid metabolism, the predominance of 18:0/20:4 acyl chains is lost. Recently, molecular mechanisms underpinning the enrichment or alteration of these acyl chains in PI lipids have begun to emerge. In the majority of the cases a common feature is the presence of enzymes bearing substrate acyl chain specificity. However, in cancer cells, it has been shown that one (not the only) of the mechanisms responsible for the loss in this acyl chain enrichment is mutation on the transcription factor p53 gene, which is one of the most highly mutated genes in cancers. There is a compelling need for a global picture of the specificity of the acyl chain composition of PIs. This can be possible once high-resolution spatio-temporal information is gathered in a cellular context; which can ultimately lead to potential novel targets to combat conditions with altered PI acyl chain profiles.
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PMID:Specificity of Acyl Chain Composition of Phosphatidylinositols. 3138 Dec 72

The classification of immune subtypes was based on immune signatures highlighting the tumor immuno-microenvironment. It was found that immune subtypes associated with mutation and expression patterns in the tumor. How the intrinsic genetic and transcriptomic alterations contribute to the immune subtypes and how to select drug combinations from both targeted drugs and immune therapeutic drugs according to different immune subtypes are still not clear. Through statistical analysis of genetic alterations and transcriptional profiles of breast invasive carcinoma (BRCA) samples, we found significant differences in the number of somatic missense mutations and frameshift deletions among the different immune subtypes. The high mutation load for somatic missense mutations and frameshift deletions may be explained by the high frequency of mutations and high expression of DNA double-strand break repair pathway genes. Extensive analysis of signaling pathways in both the genetic and transcriptomic levels reveals significantly altered pathways such as tumor protein Tumor Protein P53 (TP53) and receptor tyrosine kinase (RTK)/RAS signaling pathways among different subtypes. Drug targets in the signaling pathways such as mitogen-activated protein kinase kinase kinase 1 (MAP3K1) and Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Alpha (PIK3CA) show genetic alteration in specific subtypes, which may be potential targets for patients of a specific subtype. More drug targets which show transcriptional difference among immune subtypes were discovered, such as cyclin-dependent kinase (CDK)4, CDK6, Erb-B2 receptor tyrosine kinase 2 (ERBB2), etc. Moreover, differences in functional activity between tumor growth and immune-related pathways also elucidate the extrinsic factors of differences in prognosis and suggest potential drug combinations for different immune subtypes. These results help to explain how intrinsic alterations are associated with the immune subtypes and provide clues for possible combination therapy for different immune subtypes.
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PMID:Intrinsic Genetic and Transcriptomic Patterns Reflect Tumor Immune Subtypes Facilitating Exploring Possible Combinatory Therapy. 3239 77


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