MAF1 represses CDKN1A through a Pol III-dependent mechanism

Lee, Yu-Ling; Li, Yuan-Ching; Su, Chia-Hsin; Chiao, Chun-Hui; Lin, I-Hsuan; Hsu, Ming

doi:10.7554/elife.06283

Cited by 20 publications

(30 citation statements)

References 37 publications

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“…Convention would suggest specific protein-protein interactions with promoter-selective transcription factors, although no candidate factors have been identified thus far. An alternate possibility is that Maf1 may affect Pol II transcription either locally [64,65] or though topological domains involving long range DNA loop interactions [66]. Recent work with human monocytes has identified more than 250 direct tDNA contact domains and tDNA clusters.…”

Section: Discussionmentioning

confidence: 99%

Maf1 phenotypes and cell physiology

Willis

2018

Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanism

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As a master regulator of transcription by RNA polymerase (Pol) III, Maf1 represses the synthesis of highly abundant non-coding RNAs as anabolic signals dissipate, as the quality or quantity of nutrients decreases, and under a wide range of cellular and environmental stress conditions. Thus, Maf1 responds to changes in cell physiology to conserve metabolic energy and to help maintain appropriate levels of tRNAs and other essential non-coding RNAs. Studies in different model organisms and cell-based systems show that perturbations of Maf1 can also impact cell physiology and metabolism. These effects are mediated by changes in Pol III transcription and/or by effects of Maf1 on the expression of select Pol II-transcribed genes. Maf1 phenotypes can vary between different systems and are sometimes conflicting as in comparisons between Maf1 KO mice and cultured mammalian cells. These studies are reviewed in an effort to better appreciate the relationship between Maf1 function and cell physiology. 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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Section: Discussionmentioning

confidence: 99%

Maf1 phenotypes and cell physiology

Willis

2018

Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanism

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“…The underlying mechanism for MAF1 recruitment, in any organism, to chromatin is unknown, even more so for non-RNA pol III loci. Several models agree that MAF1 can interact with either RNA pol III itself or transcription factors to prevent transcription [5,6,10,11,16,17,24,27,28]. The expressions of pod-2/ACC1 and fasn-1/FASN are regulated by RNA pol II and SREBPs in C. elegans and mammals.…”

Section: Discussionmentioning

confidence: 99%

“…Human MAF1 has at least three TORC1 phosphorylation sites (S60/68/75) that regulate nuclear localization and function. In addition to phosphorylation, SUMOylation also impacts human MAF1 activity, without changing MAF1 localization [27], indicating that there are multiple levels of MAF1 regulation at play [28]. …”

Section: Introductionmentioning

confidence: 99%

The C-Box Region of MAF1 Regulates Transcriptional Activity and Protein Stability

Pradhan

Hammerquist

Khanna

et al. 2017

Journal of Molecular Biology

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MAF1 is a conserved negative regulator of RNA polymerase (pol) III and intracellular lipid homeostasis across species. Here, we show that the MAF1 C-box region negatively regulates its activity. Mutations in Caenorhabditis elegans mafr-1 that truncate the C-box retain the ability to inhibit the transcription of RNA pol III targets, reduce lipid biogenesis, and lower reproductive output. In human cells, C-box deletion of MAF1 leads to increased MAF1 nuclear localization and enhanced repression of ACC1 and FASN, but with impaired repression of RNA pol III targets. Surprisingly, C-box mutations render MAF1 insensitive to rapamycin, further defining a regulatory role for this region. Two MAF1 species, MAF1L and MAF1S, are regulated by the C-box YSY motif, which, when mutated, alters species stoichiometry and proteasome-dependent turnover of nuclear MAF1. Our results reveal a role for the C-box region as a critical determinant of MAF1 stability, activity, and response to cellular stress.

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“…Maf1 was also reported to induce transcription of the PTEN promoter [35]. In another example, the effect of Maf1 on specific RNA pol II genes involved changes in RNA pol III and Maf1 recruitment to a promoter-associated short interspersed element (SINE) [34]. However Maf1 does not contain a canonical DNA binding domain and there is no direct demonstration of Maf1 alone binding to DNA.…”

Section: The Transcription Factor Maf1 Functions As a Tumor Suppressormentioning

confidence: 99%