IRE1alpha controls cyclin A1 expression and promotes cell proliferation through XBP-1.

ABSTRACT: IRE1 is a conserved dual endoribonuclease/protein kinase that is indispensable for directing the endoplasmic reticulum (ER) stress response in yeast, flies, and worms. In mammalian systems, however, the precise biological activities carried out by IRE1alpha are unclear. Here, molecular and chemical genetic approaches were used to control IRE1 activity in a number of prostate cancer cell lines and the resulting impact on gene transcription, cell survival, and proliferation was examined. Modulating IRE1alpha activity had no transcriptional effect on the induction of genes classically associated with the ER stress response (Grp78 and CHOP) or cell survival when confronted with ER stress agents. Rather, IRE1alpha activity was positively correlated to proliferation. Since Xbp-1 mRNA is the sole

SUBMITTER: Thorpe JA 

PROVIDER: S-EPMC3006623 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature