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Function
The protein produced from the PTEN gene is called Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN. This protein acts a tumor suppressor. It is found to be mutated in many cancers at a high rate (1). Tumor suppressor genes in general act to keep cells from dividing uncontrollably. It can do this by inducing apoptosis or regulating cell cycle progression. This protein is a phosphatase, meaning that it dephosphorylates other proteins and fats, more specifically phosphoinositide substrates of lipids (1). This protein also inhibits cell migration and stops adhesion formation by dephosphorylating adhesion kinase (2). It acts greatly on the membrane, which then leads to apoptosis. It also affects cell movement so the cells can’t leave the area they are in, which helps prevent the cancer from metastasizing. The longer isoform of this protein is associated with the inner mitochondrial matrix and helps to regulate energy production (1). Different isoforms that are formed through alternative splicing can lead to different uses for the protein.
Disease
The diseases associated with this protein include different types of cancer, Cowden syndrome, and Bannayan-Riley-Ruvalcaba syndrome. Cowden syndrome (CS) is an autosomal dominant disease that is caused by a mutation in the PTEN gene and characterized by multiple harmatomas of different tissues as well as high risk of cancer in the breast, thyroid, kidney, endometrium and colon (4). This disease can affect anyone at any age. Bannayan-Riley-Ruvalcaba syndrome is also autosomal dominant, which is characterized by intestinal polyps, lipomas, macrocephaly and genital lentiginosis (5). This diseases age of onset is infancy or neonatal and it also increases risk for cancer as CS does (5). This gene is found mutated in multiple cancers including, prostate, primary glioblastoma, renal cell, breast and brain cancer, melanoma, and squamous cell carcinoma among others (3). Since this gene is expressed in many parts of the body, mutations can lead to many different types of cancer.
Relevance
Since mutations of this gene can cause so many different cancers and diseases it is very important that it is studied further to try and make treatments better for the diseases it causes and possible therapies for cancer. One possible treatment could be gene therapy. If the exact mutation can be pinpointed, then we could try to “fix” that gene so the mutation won’t be there anymore. If we can determine the mutation early enough, chance of remission and improvement will increase greatly.
Structural highlights
This protein is 403 amino acids long and is a monomer. Interaction with MAGI2 helps to stabilize the protein, while interaction with STK11 phosphorylates the protein (3). It requires a cofactor and for this protein the cofactor is Mg2+. Phosphorylation of PTEN inhibits activity with PIP3 (3). The interaction of the protein with other proteins and ligands helps to determine its activity in the cell.
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