Unknown

Dataset Information

0

Transcription factor Nrf1 is topologically repartitioned across membranes to enable target gene transactivation through its acidic glucose-responsive domains.


ABSTRACT: The membrane-bound Nrf1 transcription factor regulates critical homeostatic and developmental genes. The conserved N-terminal homology box 1 (NHB1) sequence in Nrf1 targets the cap'n'collar (CNC) basic basic-region leucine zipper (bZIP) factor to the endoplasmic reticulum (ER), but it is unknown how its activity is controlled topologically within membranes. Herein, we report a hitherto unknown mechanism by which the transactivation activity of Nrf1 is controlled through its membrane-topology. Thus after Nrf1 is anchored within ER membranes, its acidic transactivation domains (TADs), including the Asn/Ser/Thr-rich (NST) glycodomain situated between acidic domain 1 (AD1) and AD2, are transiently translocated into the lumen of the ER, where NST is glycosylated in the presence of glucose to yield an inactive 120-kDa Nrf1 glycoprotein. Subsequently, portions of the TADs partially repartition across membranes into the cyto/nucleoplasmic compartments, whereupon an active 95-kDa form of Nrf1 accumulates, a process that is more obvious in glucose-deprived cells and may involve deglycosylation. The repartitioning of Nrf1 out of membranes is monitored within this protein by its acidic-hydrophobic amphipathic glucose-responsive domains, particularly the Neh5L subdomain within AD1. Therefore, the membrane-topological organization of Nrf1 dictates its post-translational modifications (i.e. glycosylation, the putative deglycosylation and selective proteolysis), which together control its ability to transactivate target genes.

SUBMITTER: Zhang Y 

PROVIDER: S-EPMC3973704 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

altmetric image

Publications

Transcription factor Nrf1 is topologically repartitioned across membranes to enable target gene transactivation through its acidic glucose-responsive domains.

Zhang Yiguo Y   Ren Yonggang Y   Li Shaojun S   Hayes John D JD  

PloS one 20140402 4


The membrane-bound Nrf1 transcription factor regulates critical homeostatic and developmental genes. The conserved N-terminal homology box 1 (NHB1) sequence in Nrf1 targets the cap'n'collar (CNC) basic basic-region leucine zipper (bZIP) factor to the endoplasmic reticulum (ER), but it is unknown how its activity is controlled topologically within membranes. Herein, we report a hitherto unknown mechanism by which the transactivation activity of Nrf1 is controlled through its membrane-topology. Th  ...[more]

Similar Datasets

| S-EPMC4937343 | biostudies-literature
| S-EPMC3899380 | biostudies-literature
| S-EPMC5910229 | biostudies-literature
| S-EPMC6980758 | biostudies-literature
| S-EPMC3684815 | biostudies-literature
2019-12-04 | GSE139810 | GEO
| S-EPMC7567612 | biostudies-literature
| S-EPMC6431181 | biostudies-literature
2014-03-26 | E-GEOD-49111 | biostudies-arrayexpress
| S-EPMC4251741 | biostudies-literature