PTEN Nuclear Functions

For years, clinical and basic researchers have been aware of the presence of PTEN in the nucleus in cell culture, animal models, and both healthy and diseased human tissues.Despite the early recognition of nuclear PTEN, the understanding of the mechanisms of its nuclear localization, function in the nucleus, and importance in biology and human disease has been lacking.Over the last decade, emerging concepts for the complex involvement of nuclear PTEN in a variety of processes, including genome maintenance and DNA repair, cell-cycle control, gene expression, and DNA replication, are illuminating what could prove to be the key path toward a full understanding of PTEN function in health and disease.Dysregulation of nuclear PTEN is now considered an important aspect of the etiology of many pathologic conditions, prompting reconsideration of the therapeutic approaches aimed at countering the consequences of PTEN deficiency.This new knowledge is fueling the development of innovative therapeutic modalities for a broad spectrum of human conditions, from cancer and metabolic diseases, to neurological disorders and autism. DETECTION OF PTEN IN THE NUCLEUSS ome of the earliest detection of PTEN in tis- sue, using immunohistochemical staining of patient samples, revealed PTEN's cytoplasmic and nuclear localization and potential differential distribution of the protein in healthy and diseased cells.In addition to cytoplasmic localization, PTEN was found in the nuclei of normal breast epithelium (Perren et al. 1999), neuronal and endothelial cells (Sano et al. 1999), proliferating endometrium (Mutter et al. 2000), normal pancreatic islet cells (Perren et al. 2000), vascular smooth muscle cells (Déléris et al. 2003), and follicular thyroid cells (Gimm et al. 2000).These reports described PTEN in normal tissue nuclei, but absence in neoplastic tissue.Nuclear localization of PTEN in tissue corroborated the initial observations on nuclear and cytoplasmic localization of transfected PTEN in various cell lines (Furnari et al. 1997;Li and Sun 1997).The first study to examine the cytoplasmic nuclear partitioning of PTEN in melanoma reported that lack of nuclear PTEN was associated with a high mitotic index (Whiteman et al. 2002).Coupled with the previous findings of loss of nuclear PTEN in neoplastic tissue, these observations raised a possibility for a contribution of nuclear PTEN to tumor suppression.Nevertheless, the discovery that PTEN acts as a phosphatidylinositol-(3,4,5) and -(3,4) phosphatase and opposes PI3K signaling from the plasma membrane

Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.