title: Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) induces cancer cell senescence by interacting with telomerase RNA component.
abstract: Oxidative stress regulates telomere homeostasis and cellular aging by unclear mechanisms. Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) is a key mediator of many oxidative stress responses, involving GAPDH nuclear translocation and induction of cell death. We report here that GAPDH interacts with the telomerase RNA component (TERC), inhibits telomerase activity, and induces telomere shortening and breast cancer cell senescence. The Rossmann fold containing NAD(+) binding region on GAPDH is responsible for the interaction with TERC, whereas a lysine residue in the GAPDH catalytic domain is required for inhibiting telomerase activity and disrupting telomere maintenance. Furthermore, the GAPDH substrate glyceraldehyde-3-phosphate (G3P) and the nitric oxide donor S-nitrosoglutathione (GSNO) both negatively regulate GAPDH inhibition of telomerase activity. Thus, we demonstrate that GAPDH is regulated to target the telomerase complex, resulting in an arrest of telomere maintenance and cancer cell proliferation.
authors: Institute of Aging Research, School of Medicine,  Hangzhou Normal University, Hangzhou, Zhejiang Province 310036,  China.
authors: Craig
authors: C
authors: Nicholls
authors: Alexander Ruvantha
authors: AR
authors: Pinto
authors: He
authors: H
authors: Li
authors: Ling
authors: L
authors: Li
authors: Lihui
authors: L
authors: Wang
authors: Richard
authors: R
authors: Simpson
authors: Jun-Ping
authors: JP
authors: Liu
mesh_terms: D001943:Breast Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D016922:Cellular Senescence / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005986:Glyceraldehyde 3-Phosphate / Q000494:pharmacology; D024581:Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating) / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D009243:NAD / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects; D017434:Protein Structure, Tertiary; D012313:RNA / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D026422:S-Nitrosoglutathione / Q000494:pharmacology; D013329:Structure-Activity Relationship; D019098:Telomerase / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D059506:Telomere Shortening / Q000187:drug effects / Q000235:genetics
chemical_list: C422952:telomerase RNA; D009243:NAD; D005986:Glyceraldehyde 3-Phosphate; D049452:Green Fluorescent Proteins; D026422:S-Nitrosoglutathione; D012313:RNA; D024581:Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating); D019098:Telomerase