Beyond regulation of pol III: Role of MAF1 in growth, metabolism, aging and cancer

MAF1 was discovered as a master repressor of Pol III-dependent transcription in response to diverse extracellular signals, including growth factor, nutrient and stress. It is regulated through posttranslational mechanisms such as phosphorylation. A prominent upstream regulator of MAF1 is the mechani...

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Published in:Biochimica et biophysica acta. Gene regulatory mechanisms 2018-04, Vol.1861 (4), p.338-343
Main Authors: Zhang, Shanshan, Li, Xiaoxing, Wang, Hui-Yun, Steven Zheng, X.F.
Format: Article
Language:English
Subjects:
Aging - metabolism
Animals
Growth - physiology
Humans
MafB Transcription Factor - physiology
Metabolic Networks and Pathways
Models, Biological
Neoplasms - metabolism
Protein Domains
Protein Processing, Post-Translational
RNA Polymerase III - metabolism
Signal Transduction
TOR Serine-Threonine Kinases - physiology
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Summary:MAF1 was discovered as a master repressor of Pol III-dependent transcription in response to diverse extracellular signals, including growth factor, nutrient and stress. It is regulated through posttranslational mechanisms such as phosphorylation. A prominent upstream regulator of MAF1 is the mechanistic target of rapamycin (mTOR) pathway. mTOR kinase directly phosphorylates MAF1, controlling its localization and transcriptional activity. In mammals, MAF1 has also been shown to regulate Pol I- and Pol II-dependent transcription. Interestingly, MAF1 modulates Pol II activity both as a repressor and activator, depending on specific target genes, to impact on cellular growth and metabolism. While MAF1 represses genes such as TATA-binding protein (TBP) and fatty acid synthase (FASN), it activates the expression of PTEN, a major tumor suppressor and an inhibitor of the mTOR signaling. Increasing evidence indicates that MAF1 plays an important role in different aspects of normal physiology, lifespan and oncogenesis. Here we will review the current knowledge on MAF1 in growth, metabolism, aging and cancer. This article is part of a Special Issue entitled: SI: Regulation of tRNA synthesis and modification in physiological conditions and disease edited by Dr. Boguta Magdalena. •MAF1 is a master repressor of Pol III-dependent transcription.•MAF1 also regulates Pol I- and Pol II-dependent transcription through diverse mechanisms.•MAF1 suppresses tumorigenesis by inhibiting cell growth and metabolism.
ISSN:1874-9399
1876-4320
DOI:10.1016/j.bbagrm.2018.01.019