Year: 2013
Type: article
Abstract: Telomeres are specialized structures at the ends of eukaryotic chromosomes that are important for maintaining genome stability and integrity. Telomere dysfunction has been linked to aging and cancer development. In mammalian cells, extensive studies have been carried out to illustrate how core telomeric proteins assemble on telomeres to recruit the telomerase and additional factors for telomere maintenance and protection. In comparison, how changes in growth signaling pathways impact telomeres and telomere-binding proteins remains largely unexplored. The phosphatidylinositol 3-kinase (PI3-K)/Akt (also known as PKB) pathway, one of the best characterized growth signaling cascades, regulates a variety of cellular function including cell proliferation, survival, metabolism, and DNA repair, and dysregulation of PI3-K/Akt signaling has been linked to aging and diseases such as cancer and diabetes. In this study, we provide evidence that the Akt signaling pathway plays an important role in telomere protection. Akt inhibition either by chemical inhibitors or small interfering RNAs induced telomere dysfunction. Furthermore, we found that TPP1 could homodimerize through its OB-fold, a process that was dependent on the Akt kinase. Telomere damage and reduced TPP1 dimerization as a result of Akt inhibition was also accompanied by diminished recruitment of TPP1 and POT1 to the telomeres. Our findings highlight a previously unknown link between Akt signaling and telomere protection.
Source: Aging Cell
DOI: 10.1111/acel.12137
Authors: Xin Han, Dan Liu, Yi Zhang, Yujing Li, Weisi Lu, Junjie Chen, Zhou Songyang
Language: English
Subfield: Physiology (medical)
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Funders: Welch Foundation, Dan L. Duncan Cancer Center, Baylor College of Medicine, National Institutes of Health, Intellectual and Developmental Disabilities Research Center, National Key Research and Development Program of China, Specialized Research Fund for the Doctoral Program of Higher Education of China, National Cancer Institute, National Institute of General Medical Sciences, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: Mechanism and Consequences of Telomere Dysfunction, Defining the human telomere signaling networks and their implication in cancer, Baylor Intellectual and Developmental Disabilities Research Center, G5508324684, G6609870569, G7249548785, G7632877781, G8312539453, Baylor College of Medicine Cancer Center - Cancer Center Support Grant
OpenAlex ID: W2042209788