Open AccessAkt regulates TPP 1 homodimerization and telomere protection
Author(s) -
Han Xin,
Liu Dan,
Zhang Yi,
Li Yujing,
Lu Weisi,
Chen Junjie,
Songyang Zhou
Publication year - 2013
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/acel.12137
Subject(s) - telomere , protein kinase b , biology , telomerase , microbiology and biotechnology , signal transduction , pi3k/akt/mtor pathway , dna damage , proto oncogene proteins c akt , kinase , cancer research , genetics , dna , gene
Summary 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 ( PI 3‐ K )/ A kt (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 PI 3‐ K / A kt signaling has been linked to aging and diseases such as cancer and diabetes. In this study, we provide evidence that the A kt signaling pathway plays an important role in telomere protection. A kt inhibition either by chemical inhibitors or small interfering RNA s induced telomere dysfunction. Furthermore, we found that TPP 1 could homodimerize through its OB ‐fold, a process that was dependent on the A kt kinase. Telomere damage and reduced TPP 1 dimerization as a result of A kt inhibition was also accompanied by diminished recruitment of TPP 1 and POT 1 to the telomeres. Our findings highlight a previously unknown link between A kt signaling and telomere protection.