TY - JOUR
T1 - Beyond regulation of pol III
T2 - Role of MAF1 in growth, metabolism, aging and cancer
AU - Zhang, Shanshan
AU - Li, Xiaoxing
AU - Wang, Hui Yun
AU - Steven Zheng, X. F.
N1 - Funding Information:
This work was supported by the National Institutes of Health ( R01CA173519 ), the National Natural Science Foundation of China (No: 81730081 , 81572440 , 81372600 and 81572466 ), the Recruitment Program of Global Experts (No: 84000-18821102 ), the Leading Talent of Guangdong Province , the Natural Science Foundation of Guangdong Province for Distinguished Young Scholar (No: 2015A030306047 ) and the Research Fund of State Key Laboratory of Oncology in South China (No: 012210 ).
Publisher Copyright:
© 2018
PY - 2018/4
Y1 - 2018/4
N2 - 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.
AB - 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.
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U2 - 10.1016/j.bbagrm.2018.01.019
DO - 10.1016/j.bbagrm.2018.01.019
M3 - Review article
C2 - 29407795
AN - SCOPUS:85042004728
SN - 1874-9399
VL - 1861
SP - 338
EP - 343
JO - Biochimica et Biophysica Acta - Gene Regulatory Mechanisms
JF - Biochimica et Biophysica Acta - Gene Regulatory Mechanisms
IS - 4
ER -