title: Integration of the metabolic/redox state, histone gene switching, DNA replication and S-phase progression by moonlighting metabolic enzymes.
abstract: The concept of one-protein-multiple-function, i.e. moonlighting proteins, is an ever-expanding paradigm. We obtained compelling evidence that an array of 'cytoplasmic' metabolic enzymes can enter the nuclei to carry out moonlighting transcription functions; this phenomenon is conserved from Drosophila to humans. Of particular interest are the classical glycolytic enzymes GAPDH (glyceraldehyde-3-phosphate dehydrogenase) and LDH (lactate dehydrogenase), which utilize NAD(H) as coenzymes and not only moonlight (in their nuclear forms) to regulate the transcription of S-phase-specific histone genes, but also act as metabolic/redox sensors that link histone gene switching to DNA replication and S-phase progression.
authors.affiliation: *College of Biotechnology, Tianjin University of Science and Technology, No. 29, 13th Avenue, TEDA, Tianjin 300457, People's Republic of China.
authors.forename: Hongpeng
authors.initials: H
authors.lastname: He
authors.affiliation: †Institute of Molecular and Cell Biology, 61 Biopolis Drive, Proteos, Singapore 138673, Singapore.
authors.forename: Mei-Chin
authors.initials: MC
authors.lastname: Lee
authors.affiliation: ‡School of Basic Medical Sciences, Zhejiang University College of Medicine, No. 388, YuHangTang Road, Hangzhou, Zhejiang 310058, People's Republic of China.
authors.forename: Li-Ling
authors.initials: LL
authors.lastname: Zheng
authors.affiliation: §Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21230, U.S.A.
authors.forename: Lei
authors.initials: L
authors.lastname: Zheng
authors.affiliation: ‡School of Basic Medical Sciences, Zhejiang University College of Medicine, No. 388, YuHangTang Road, Hangzhou, Zhejiang 310058, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Luo
mesh_terms: D002467:Cell Nucleus / Q000201:enzymology* / Q000235:genetics; D003593:Cytoplasm / Q000201:enzymology* / Q000235:genetics; D004261:DNA Replication / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D009243:NAD / Q000378:metabolism; D010084:Oxidation-Reduction; D016196:S Phase / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; D006657:Histones; D009243:NAD; D007770:L-Lactate Dehydrogenase; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases