Creighton University School of Medicine, Department of Biomedical Sciences, Omaha, NE 68178, USA.
Expert Opin Ther Pat. 2013 May;23(5):569-80. doi: 10.1517/13543776.2013.768985. Epub 2013 Feb 5.
PTEN (phosphatase and tensin homolog deleted on chromosome 10) plays a pivotal role in controlling intracellular signaling for cell survival and proliferation by inhibiting the PI3K/Akt pathway, and its dysfunction is associated with several neoplastic diseases. PTEN is frequently found mutated in many pathological conditions highlighting its importance in normal physiological function. Unlike several cellular proteins which are activated by phosphorylation, PTEN is inactivated upon phosphorylation by specific kinases which phosphorylate serine and threonine residues in its C-terminal region. Therefore, development of therapeutic agents that specifically target kinases and kinase-domain-containing proteins affecting PTEN would lead to the treatment of PTEN-related diseases.
With increasing evidence on the role of PTEN in many human diseases, the present review focuses on the clinical relevance of PTEN with a comprehensive list of currently identified modulators of PTEN, and proposes potentially novel molecular targets which could aid in the development of drug candidates for the treatment of PTEN-related diseases such as cardiovascular diseases, diabetes, obesity, cancer, autism, Parkinson's and Alzheimer's diseases.
This review describes several target sites that could help in the development of novel drug candidates to regulate or restore the normal physiological functions of PTEN and are essential in the treatment of human diseases where PTEN plays a pivotal role.
PTEN（第 10 号染色体缺失的磷酸酶及张力蛋白同源物）通过抑制 PI3K/Akt 通路，在控制细胞存活和增殖的细胞内信号中起着关键作用，其功能障碍与多种肿瘤性疾病有关。PTEN 在许多病理条件下经常发生突变，突出了其在正常生理功能中的重要性。与许多通过磷酸化激活的细胞蛋白不同，PTEN 会在其 C 末端区域的特定激酶使丝氨酸和苏氨酸残基磷酸化时失活。因此，开发专门针对影响 PTEN 的激酶和含激酶结构域的蛋白质的治疗剂将导致针对与 PTEN 相关的疾病的治疗。
随着越来越多的证据表明 PTEN 在许多人类疾病中的作用，本综述重点关注 PTEN 的临床相关性，列出了目前已确定的 PTEN 调节剂的综合清单，并提出了潜在的新分子靶点，这些靶点可能有助于开发用于治疗与 PTEN 相关疾病（如心血管疾病、糖尿病、肥胖症、癌症、自闭症、帕金森病和阿尔茨海默病）的药物候选物。
本综述描述了几个可能有助于开发调节或恢复 PTEN 正常生理功能的新型药物候选物的靶点，对于治疗 PTEN 起关键作用的人类疾病至关重要。
