This Article Full Text Full Text (PDF) Other Versions of this Article: MCB.01866-07v1 28/7/2235    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Copyright Information Books from ASM Press MicrobeWorld Google Scholar Articles by Bailey, C. M. Articles by Hendrix, M. J. C. PubMed PubMed Citation Articles by Bailey, C. M. Articles by Hendrix, M. J. C.

Interferon Regulatory Factor 6 Promotes Cell Cycle Arrest and Is Regulated by the Proteasome in a Cell Cycle-Dependent Manner

Children's Memorial Research Center,¹ Robert H. Lurie Comprehensive Cancer Center,² Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois³

Received 12 October 2007/ Returned for modification 9 November 2007/ Accepted 15 January 2008

Interferon regulatory factor 6 (IRF6) is a novel and unique member of the IRF family of transcription factors. IRF6 has not been linked to the regulatory pathways or functions associated with other IRF family members, and the regulation and function of IRF6 remain unknown. We recently identified a protein interaction between IRF6 and the tumor suppressor maspin. To gain insight into the biological significance of the maspin-IRF6 interaction, we examined the regulation and function of IRF6 in relation to maspin in normal mammary epithelial cells. Our results demonstrate that in quiescent cells, IRF6 exists primarily in a nonphosphorylated state. However, cellular proliferation leads to rapid IRF6 phosphorylation, resulting in proteasome-dependent IRF6 degradation. These data are supported in situ by the increased expression of IRF6 in quiescent, differentiated lobuloalveolar cells of the lactating mammary gland compared to its expression in proliferating ductal and glandular epithelial cells during pregnancy. Furthermore, the reexpression of IRF6 in breast cancer cells results in cell cycle arrest, and the presence of maspin augments this response. These data support a model in which IRF6, in collaboration with maspin, promotes mammary epithelial cell differentiation by facilitating entry into the G₀ phase of the cell cycle.

Published ahead of print on 22 January 2008.