Integration of the metabolic/redox state, histone gene switching, DNA replication and S-phase progression by moonlighting metabolic enzymes

Author:

He Hongpeng1,Lee Mei-Chin2,Zheng Li-Ling3,Zheng Lei4,Luo Yan3

Affiliation:

1. College of Biotechnology, Tianjin University of Science and Technology, No. 29, 13th Avenue, TEDA, Tianjin 300457, People's Republic of China

2. Institute of Molecular and Cell Biology, 61 Biopolis Drive, Proteos, Singapore 138673, Singapore

3. School of Basic Medical Sciences, Zhejiang University College of Medicine, No. 388, YuHangTang Road, Hangzhou, Zhejiang 310058, People's Republic of China

4. Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21230, U.S.A.

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.

Publisher

Portland Press Ltd.

Subject

Cell Biology,Molecular Biology,Biochemistry,Biophysics

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