Telomere maintenance is essential for continued cell proliferation and chromosome stability. Telomeres are maintained by telomerase and a collection of associated proteins. The telomeric protein telomeric repeat binding factor 1 (TRF1) negatively regulates telomere length by inhibiting access of telomerase at telomere termini. Here we report that TRF1 interacts with the beta subunit of casein kinase 2 (CK2) and serves as a substrate for CK2. CK2-mediated phosphorylation is required for the efficient telomere binding of TRF1 in vitro and in vivo. Inhibition of CK2 by the CK2 inhibitor 5,6-dichloro-1-beta-d-ribofuranosylbenzimidazole decreased the ability of TRF1 to bind telomeric DNA. The resulting telomere-unbound form of TRF1 was then ubiquitinated and degraded by the proteasome. Partial knockdown of CK2 by small interfering RNA resulted in removal of TRF1 from telomeres and subsequent degradation of TRF1. Mapping of the CK2 target site identified threonine 122 as a substrate in TRF1. A threonine to alanine change at this position led to a diminished DNA binding due to reduced dimerization of TRF1. In addition, phosphorylation of threonine 122 seemed critical for TRF1-mediated telomere length control. Our findings suggest that CK2-mediated phosphorylation of TRF1 plays an important role in modulating telomere length homeostasis by determining the levels of TRF1 at telomeres.
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http://dx.doi.org/10.1074/jbc.M710065200 | DOI Listing |
Fertil Steril
January 2025
Division of Reproductive Endocrinology & Infertility, University of California, San Francisco.
Objective: To study measures of endothelial health, cardiovascular risk, and cellular aging between PCOS patients and a reproductive age normative cohort.
Design: Cross-sectional study.
Subjects: Community-based PCOS patients and a normative ovarian aging cohort as controls, aged 45 or younger at the time of evaluation.
World J Gastrointest Oncol
January 2025
Department of Clinical Laboratory, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, Sichuan Province, China.
Background: Esophageal squamous cell carcinoma (ESCC) is a malignant tumor with high morbidity and mortality, and easy to develop resistance to chemotherapeutic agents. Telomeres are DNA-protein complexes located at the termini of chromosomes in eukaryotic cells, which are unreplaceable in maintaining the stability and integrity of genome. Telomerase, an RNA-dependent DNA polymerase, play vital role in telomere length maintain, targeting telomerase is a promising therapeutic strategy for cancer.
View Article and Find Full Text PDFOpen Access J Sports Med
January 2025
Prodia Clinical Laboratory, Jakarta, Indonesia.
Background: Sarcopenia is characterized by the progressive loss of skeletal muscle mass and poses a significant health challenge for older adults by increasing the risk of disability and decreasing quality of life. Yoga considers as a low-risk and beneficial exercise for older adults. This research aims to evaluate the potential of yoga practice as a preventive strategy against sarcopenia in Indonesian older adults.
View Article and Find Full Text PDFJ Bras Pneumol
January 2025
. Departamento de Biologia Geral, Universidade Federal Fluminense, Niterói (RJ) Brasil.
Objective: Silicosis is a pneumoconiosis characterized by fibrosis of the lung parenchyma caused by the inhalation of silica particles. Silica dust inhalation is associated with inflammation and induction of oxidative stress in the lungs. This oxidative stress affects telomeres, which are short tandem DNA repeats that cap the end of linear chromosomes.
View Article and Find Full Text PDFMedicine (Baltimore)
November 2024
State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, National Clinical Research Center of Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.
Pulmonary arterial hypertension (PAH) is a life-threatening condition characterized by elevated pulmonary artery pressure, leading to right heart failure, and mortality. The role of telomere length, a marker of biological aging, in PAH remains unclear. We utilized summary-level data from genome-wide association studies for various measures of telomere length and PAH.
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