Luman is capable of binding and activating transcription from the unfolded protein response element.
Luman (or LZIP, CREB3) is a transcription factor with an endoplasmic reticulum (ER)-transmembrane domain. Due to its structural similarities with ATF6, it is thought that Luman might also be involved in cellular stress responses. Here we report that Luman can bind and activate transcription from the consensus unfolded protein response element (UPRE). Mutations that disrupted the binding of Luman to the UPREs impaired its ability to activate transcription from these sites. Overexpression of Luman stimulated transcription of EDEM, a downstream effector of the mammalian unfolded protein response involved in ER-associated degradation (ERAD). Unlike ATF6, however, Luman was not activated by proteolytic cleavage in response to endoplasmic reticulum stressors such as tunicamycin and thapsigargin. These results suggest that the activation of ERAD by Luman is likely through a pathway different from the common ER stress response, and that additional factor(s) are required for the activation of this Luman-mediated pathway.
DenBoer
Lisa M
LM
Department of Molecular and Cellular Biology, University of Guelph, Ont., Canada N1G 2W1.
Hardy-Smith
Philip W
PW
Hogan
Melissa R
MR
Cockram
Gregory P
GP
Audas
Timothy E
TE
Lu
Rui
R
D001665:Binding Sites; D016384:Consensus Sequence; D017362:Cyclic AMP Response Element-Binding Protein; D004721:Endoplasmic Reticulum / Q000187:drug effects; D006801:Humans; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics; D009154:Mutation; D017510:Protein Folding; D012333:RNA, Messenger / Q000096:biosynthesis; D020218:Response Elements; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation
C107941:CREB3 protein, human; D017362:Cyclic AMP Response Element-Binding Protein; D008565:Membrane Proteins; D012333:RNA, Messenger; D014157:Transcription Factors