RRC ID 53383
Author Pradhan A, Hammerquist AM, Khanna A, Curran SP.
Title The C-Box Region of MAF1 Regulates Transcriptional Activity and Protein Stability.
Journal J Mol Biol
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.
Volume 429(2)
Pages 192-207
Published 2017-1-20
DOI 10.1016/j.jmb.2016.12.012
PII S0022-2836(16)30541-1
PMID 27986570
PMC PMC5480515
MeSH Animals Caenorhabditis elegans / genetics Caenorhabditis elegans Proteins / genetics* Caenorhabditis elegans Proteins / metabolism Gene Expression Regulation HEK293 Cells Hep G2 Cells Homeostasis Humans Protein Stability* RNA Polymerase III / metabolism* Repressor Proteins / genetics* Repressor Proteins / metabolism Sirolimus / pharmacology Transcriptional Activation*
IF 4.894
Times Cited 8
C.elegans tm6082