Telomerase consists of the catalytic subunit Telomerase Reverse Transcriptase (TERT) and the Telomerase RNA Component. Its canonical function is the prevention of telomere erosion. Over the last years it became evident that TERT is also present in tissues with low replicative potential. Important non-canonical functions of TERT are protection against apoptosis and maintenance of the cellular redox homeostasis in cancer as well as in somatic tissues. Intriguingly, TERT and reactive oxygen species (ROS) are interdependent on each other, with TERT being regulated by changes in the redox balance and itself controlling ROS levels in the cytosol and in the mitochondria. The latter is achieved because TERT is present in the mitochondria, where it protects mitochondrial DNA and maintains levels of anti-oxidative enzymes. Since numerous diseases are associated with oxidative stress, increasing the mitochondrial TERT level could be of therapeutic value.
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http://dx.doi.org/10.1016/j.redox.2020.101543 | DOI Listing |
PLoS One
January 2025
Department of Biotechnology and Bioengineering, Chonnam National University, Gwangju, Republic of Korea.
With the advancement of genetic code expansion, the field is progressing towards incorporating multiple non-canonical amino acids (ncAAs). The specificity of aminoacyl-tRNA synthetases (aaRSs) towards ncAAs is a critical factor, as engineered aaRSs frequently show polyspecificity, complicating the precise incorporation of multiple ncAAs. To address this challenge, predicting binding affinity can be beneficial.
View Article and Find Full Text PDFChembiochem
January 2025
University of Pittsburgh, Department of Chemistry, 219 Parkman Ave., 15260, Pittsburgh, UNITED STATES OF AMERICA.
The α-helix is an abundant and functionally important element of protein secondary structure, which has motivated intensive efforts toward chemical strategies to stabilize helical folds. One such method is the incorporation of non-canonical backbone composition through an additional methyl substituent at the Cα atom. Examples of monomers include the achiral 2-aminoisobutyric acid (Aib) with geminal dimethyl substitution and chiral analogues with one methyl and one non-methyl substituent.
View Article and Find Full Text PDFJ Cancer Prev
December 2024
Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, Korea.
Prolyl hydroxylase domain 2 (PHD2) is the primary oxygen sensing enzyme involved in hydroxylation of hypoxia-inducible factor (HIF). Under normoxic conditions, PHD2 hydroxylates specific proline residues in HIF-1α and HIF-2α, promoting their ubiquitination and subsequent proteasomal degradation. Although PHD2 activity decreases in hypoxia, notable residual activity persists, but its function in these conditions remains unclear Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) targets proteins with phosphorylated serine/threonine-proline (pSer/Thr-Pro) motifs.
View Article and Find Full Text PDFNat Commun
January 2025
Zhejiang Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang Key Laboratory of Frontier Medical Research on Cancer Metabolism, Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, China.
Liver fibrosis is a critical liver disease that can progress to more severe manifestations, such as cirrhosis, yet no effective targeted therapies are available. Here, we identify that ATF4, a master transcription factor in ER stress response, promotes liver fibrosis by facilitating a stress response-independent epigenetic program in hepatic stellate cells (HSCs). Unlike its canonical role in regulating UPR genes during ER stress, ATF4 activates epithelial-mesenchymal transition (EMT) gene transcription under fibrogenic conditions.
View Article and Find Full Text PDFJ Hepatol
January 2025
Department of Surgery, Sir Y.K. Pao Centre for Cancer, The Chinese University of Hong Kong, Shatin, Hong Kong, China. Electronic address:
Background & Aims: The ubiquitin receptor ADRM1/Rpn13 governs the specificity of eukaryotic protein degradation. By SMRT sequencing, we first discovered a novel spliced variant of ADRM1 with a skipped exon 9, termed ADRM1-ΔEx9, in human hepatocellular carcinoma (HCC). This study aimed to elucidate this novel ubiquitin receptor's underlying biology and clinical implications in HCC.
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