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Molecular and Cellular Biology, June 2008, p. 3952-3966, Vol. 28, No. 12
0270-7306/08/$08.00+0     doi:10.1128/MCB.01439-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

A Novel Protein, Luman/CREB3 Reruitment Factor, Inhibits Luman Activation of the Unfolded Protein Response{triangledown}

Timothy E. Audas, Yu Li, Genqing Liang, and Rui Lu*

Department of Molecular and Cellular Biology, University of Guelph, Guelph, Ontario, Canada N1G 2W1

Received 10 August 2007/ Returned for modification 4 October 2007/ Accepted 25 March 2008

Luman/CREB3 (also called LZIP) is an endoplasmic reticulum (ER)-bound cellular transcription factor. It has been implicated in the mammalian unfolded protein response (UPR), as well as herpes simplex virus reactivation from latency in sensory neurons. Here, we report the identification of a novel Luman recruitment factor (LRF). Like Luman, LRF is a UPR-responsive basic-region leucine zipper protein that is prone to proteasomal degradation. Being a highly unstable protein, LRF interacts with Luman through the leucine zipper region and promotes Luman degradation. LRF was found to recruit the nuclear form of Luman to discrete nuclear foci, which overlap with the nuclear receptor coactivator GRIP1 bodies, and repress the transactivation activity of Luman. Compared to LRF+/+ mouse embryonic fibroblast (MEF) cells, the levels of CHOP, EDEM, and Herp were elevated in LRF–/– MEF cells. We propose that LRF is a negative regulator of the UPR. For Luman, it may represent another level of regulation following Luman proteolytic cleavage on the ER and nuclear translocation. In addition to inducing rapid Luman turnover, LRF may repress the transactivation potential of Luman by sequestering it in the LRF nuclear bodies away from key cofactors (such as HCF-1) that are required for transcriptional activation.

* Corresponding author. Mailing address: Department of Molecular and Cellular Biology, University of Guelph, Guelph, ON, Canada N1G 2W1. Phone: (519) 824-4120, ext. 56247. Fax: (519) 837-2075. E-mail: rlu{at}uoguelph.ca

{triangledown} Published ahead of print on 7 April 2008.

Molecular and Cellular Biology, June 2008, p. 3952-3966, Vol. 28, No. 12
0270-7306/08/$08.00+0     doi:10.1128/MCB.01439-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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