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

Abstract：

: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.

journal_name

J Mol Biol

journal_title

Journal of molecular biology

authors

Pradhan A,Hammerquist AM,Khanna A,Curran SP

doi

10.1016/j.jmb.2016.12.012

subject

Has Abstract

pub_date

2017-01-20 00:00:00

pages

192-207

issue

2

eissn

0022-2836

issn

1089-8638

pii

S0022-2836(16)30541-1

journal_volume

429

pub_type

杂志文章

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