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DIMERIZATION IS REQUIRED FOR THE TRANSACTIVATION FUNCTION OF LUMAN BUT NOT FOR ITS ACTIVATION BY PROTEOLYTIC CLEAVAGE

Luman (LZIP/CREB3) is a basic leucine zipper (bZIP) transcription factor that has been linked to the endoplasmic reticulum (ER) stress response. In the event of ER stress, Luman is proteolytically cleaved, or ‘activated’, through regulated intramembrane proteolysis (RIP), resulting in an amino-terminal fragment that translocates to the nucleus to activate transcription of downstream unfolded protein response (UPR)-related genes. The general mode of activation of the key signal transducers of the UPR appears to be an alteration of their oligomeric states. Structural and functional similarities to these proteins suggest that Luman may be activated in a similar manner.
In this thesis, we demonstrate through in vitro and in vivo studies that Luman can form homodimers in the cell. Through the use of mutagenesis, we show that Luman dimerization is mediated through the leucine zipper and we provide evidence that Luman dimerization is required for its transcription activation function. However, we found that Luman dimerization is not required for its activation by proteolytic cleavage.

Identiferoai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:OGU.10214/3206
Date21 December 2011
CreatorsMcCluggage, Adam Robert Russell
ContributorsLu, Ray
Source SetsLibrary and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada
LanguageEnglish
Detected LanguageEnglish
TypeThesis
Rightshttp://creativecommons.org/licenses/by-sa/2.5/ca/

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