Abstract
Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a tumor suppressor gene frequently found to be inactivated in over 30% of human cancers. PTEN encodes a 54-kDa lipid phosphatase that serves as a gatekeeper of the phosphoinositide 3-kinase pathway involved in the promotion of multiple pro-tumorigenic phenotypes. Although the PTEN protein plays a pivotal role in carcinogenesis, cumulative evidence has implicated it as a key signaling molecule in several other diseases as well, such as diabetes, Alzheimer’s disease, and autism spectrum disorders. This finding suggests that diverse cell types, especially differentiated cells, express PTEN. At the cellular level, PTEN is widely distributed in all subcellular compartments and organelles. Surprisingly, the cytoplasmic compartment, not the plasma membrane, is the predominant subcellular location of PTEN. More recently, the finding of a secreted ‘long’ isoform of PTEN and the presence of PTEN in the cell nucleus further revealed unexpected biological functions of this multifaceted molecule. At the regulatory level, PTEN activity, stability, and subcellular distribution are modulated by a fascinating array of post-translational modification events, including phosphorylation, ubiquitination, and sumoylation. Dysregulation of these regulatory mechanisms has been observed in various human diseases. In this review, we provide an up-to-date overview of the knowledge gained in the last decade on how different functional domains of PTEN regulate its biological functions, with special emphasis on its subcellular distribution. This review also highlights the findings of published studies that have reported how mutational alterations in specific PTEN domains can lead to pathogenesis in humans.
Highlights
Phosphatase and TENsin homolog deleted on chromosome 10 (PTEN) was originally discovered as a bona fide tumor suppressor gene on human chromosome 10q23.3, a region frequently lost in prostate cancer and glioblastoma multiforme [1,2,3]
It is believed that PTEN belongs to a class of molecules containing the protein tyrosine phosphatase (PTP)-C2 superdomain that was formed prior to the fungi, plant, an up-to-date overview of the functional domains of PTEN involved in the regulation of its and animal kingdom divergence [19]
Similar to other dual-specificity phosphatase (DSP) and PTPs, PTEN harbors a HCXXGXXR signature motif residues 123 and 130, which is referred to as the P loop located at the bottom region of the active between residues 123 and 130, which is referred to as the P loop located at the bottom region of the site
Summary
Phosphatase and TENsin homolog deleted on chromosome 10 (PTEN) was originally discovered as a bona fide tumor suppressor gene on human chromosome 10q23.3, a region frequently lost in prostate cancer and glioblastoma multiforme [1,2,3]. PTEN is unique in the respect that the loss of its single allele can lead to carcinogenesis This haploinsufficiency of the PTEN gene has been shown to promote prostate cancer [6,7]. The protein terminates in a four-amino acid otein–protein interaction domain called the PDZ-binding motif (PDZ-BM)[17,18]. It is believed that PTEN belongs to a class of molecules containing the protein tyrosine phosphatase (PTP)-C2 superdomain that was formed prior to the fungi, plant, an up-to-date overview of the functional domains of PTEN involved in the regulation of its and animal kingdom divergence [19]. With special emphasis on its role in different subcellular compartments
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
