What does PTEN do insulin?
As a metabolic regulator, PTEN controls the metabolism of both glucose and fatty acids. These effects of PTEN through targeting the PI3K/AKT dependent and independent pathways lead to suppressed insulin sensitivity and inhibited cell growth and survival.
How is PTEN activated?
PTEN works in direct opposition to PI3K, dephosphorylating PIP3 to PIP2. AKT binds to PIP3 and is activated by phosphorylation on threonine (T)308 by PDK1 and serine (S)473 by mTORC2. AKT phosphorylates and inactivates many downstream targets, resulting in increased cellular survival and proliferation.
What is PTEN pathway?
PTEN/PI3K/AKT constitutes an important pathway regulating the signaling of multiple biological processes such as apoptosis, metabolism, cell proliferation and cell growth. PTEN is a dual protein/lipid phosphatase which main substrate is the phosphatidyl-inositol,3,4,5 triphosphate (PIP3), the product of PI3K.
Is PTEN phosphatase?
Phosphatase and tensin homolog deleted on chromosome ten (PTEN) is a phosphatase that is frequently altered in cancer. PTEN has phosphatase-dependent and – independent roles; and genetic alterations in PTEN lead to deregulation of protein synthesis, cell cycle, migration, growth, DNA repair, and survival signaling.
What enzyme does PTEN make?
PTEN protein acts as a phosphatase to dephosphorylate phosphatidylinositol (3,4,5)-trisphosphate (PtdIns (3,4,5)P3 or PIP3). PTEN specifically catalyses the dephosphorylation of the 3` phosphate of the inositol ring in PIP3, resulting in the biphosphate product PIP2 (PtdIns(4,5)P2).
How is PTEN regulated?
PTEN is under extensive regulation by miRNAs. Specific miRNAs target mRNAs by binding to miRNA response elements usually located at the 3′ untranslated region (UTR) of target mRNAs121. A number of miRNAs have been found to participate in the regulation of metabolic disease and cancer by targeting PTEN122,123 (Fig.
What enzyme produces PTEN?
PTEN acts as a tumor suppressor gene through the action of its phosphatase protein product. This phosphatase is involved in the regulation of the cell cycle, preventing cells from growing and dividing too rapidly.
What is PTEN deficiency?
PTEN-deficient tumors are characterized by (i) reduced levels of cytotoxic T cells, helper T cells and NK cells, (ii) elevated pro-oncogenic inflammatory cytokines like CCL2 and (iii) increased levels of immunosuppressive cells such as MDSCs and Tregs.
What causes PTEN mutation?
A PTEN genetic mutation can be inherited from your parents, or acquired later in life from the environment or from a mistake that happens in your body during cell division. An inherited PTEN mutation can cause a variety of health disorders. Some of these can start at infancy or early childhood.
Is there a cure for PTEN?
Currently there are no cancer treatments approved specifically for people with a PTEN mutation, nor guidelines for treating cancer specifically for people with an inherited PTEN mutation. However, experts are conducting research studies to learn which treatments may work best for people with a PTEN mutation.
What happens if PTEN is mutated?
If you have a PTEN genetic mutation, it can cause the growth of noncancerous tumors called hamartomas. Hamartomas can show up throughout the body. The mutation can also lead to the development of cancerous tumors.
How is PTEN mutation treated?
Some cancers caused by PTEN mutations may be treated with targeted therapy. Targeted therapies attack specific areas or substances in cancer cells. These therapies may be more effective and cause fewer side effects than traditional chemotherapy.
Is PTEN a rare disease?
Rarely, people with PTEN hamartoma tumor syndrome develop a type of brain tumor called cerebellar dysplastic gangliocytoma (also called adult-onset Lhermitte-Duclos disease). The exact risk of developing this type of tumor is unknown because it is so rare.
How does PTEN suppress tumor growth?
A series of publications over the past year now suggest a mechanism by which PTEN loss of function results in tumors. PTEN appears to negatively control the phosphoinositide 3-kinase signaling pathway for regulation of cell growth and survival by dephosphorylating the 3 position of phosphoinositides.