Keratin-dependent regulation of Aire and gene expression in skin tumor keratinocytes

Ryan P. Hobbs, Daryle J. Depianto, Justin T. Jacob, Minerva C. Han, Byung Min Chung, Adriana S. Batazzi, Brian G. Poll, Yajuan Guo, Jingnan Han, Sufey Ong, Wenxin Zheng, Janis M Taube, Daniela Cihakova, Fengyi Wan, Pierre A. Coulombe

Research output: Contribution to journalArticle

Abstract

Expression of the intermediate filament protein keratin 17 (K17) is robustly upregulated in inflammatory skin diseases and in many tumors originating in stratified and pseudostratified epithelia. We report that autoimmune regulator (Aire), a transcriptional regulator, is inducibly expressed in human and mouse tumor keratinocytes in a K17-dependent manner and is required for timely onset of Gli2-induced skin tumorigenesis in mice. The induction of Aire mRNA in keratinocytes depends on a functional interaction between K17 and the heterogeneous nuclear ribonucleoprotein hnRNP K. Further, K17 colocalizes with Aire protein in the nucleus of tumor-prone keratinocytes, and each factor is bound to a specific promoter region featuring an NF-κ B consensus sequence in a relevant subset of K17-and Aire-dependent proinflammatory genes. These findings provide radically new insight into keratin intermediate filament and Aire function, along with a molecular basis for the K17-dependent amplification of inflammatory and immune responses in diseased epithelia.

Original languageEnglish (US)
Pages (from-to)933-938
Number of pages6
JournalNature Genetics
Volume47
Issue number8
DOIs
StatePublished - Aug 30 2015

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Keratin-17
Regulator Genes
Keratins
Keratinocytes
Gene Expression
Skin
Heterogeneous-Nuclear Ribonucleoprotein K
Neoplasms
Epithelium
Intermediate Filament Proteins
Intermediate Filaments
Consensus Sequence
Skin Diseases
Genetic Promoter Regions
Carcinogenesis
Messenger RNA

ASJC Scopus subject areas

  • Genetics

Cite this

Hobbs, R. P., Depianto, D. J., Jacob, J. T., Han, M. C., Chung, B. M., Batazzi, A. S., ... Coulombe, P. A. (2015). Keratin-dependent regulation of Aire and gene expression in skin tumor keratinocytes. Nature Genetics, 47(8), 933-938. https://doi.org/10.1038/ng.3355

Keratin-dependent regulation of Aire and gene expression in skin tumor keratinocytes. / Hobbs, Ryan P.; Depianto, Daryle J.; Jacob, Justin T.; Han, Minerva C.; Chung, Byung Min; Batazzi, Adriana S.; Poll, Brian G.; Guo, Yajuan; Han, Jingnan; Ong, Sufey; Zheng, Wenxin; Taube, Janis M; Cihakova, Daniela; Wan, Fengyi; Coulombe, Pierre A.

In: Nature Genetics, Vol. 47, No. 8, 30.08.2015, p. 933-938.

Research output: Contribution to journalArticle

Hobbs, RP, Depianto, DJ, Jacob, JT, Han, MC, Chung, BM, Batazzi, AS, Poll, BG, Guo, Y, Han, J, Ong, S, Zheng, W, Taube, JM, Cihakova, D, Wan, F & Coulombe, PA 2015, 'Keratin-dependent regulation of Aire and gene expression in skin tumor keratinocytes', Nature Genetics, vol. 47, no. 8, pp. 933-938. https://doi.org/10.1038/ng.3355
Hobbs RP, Depianto DJ, Jacob JT, Han MC, Chung BM, Batazzi AS et al. Keratin-dependent regulation of Aire and gene expression in skin tumor keratinocytes. Nature Genetics. 2015 Aug 30;47(8):933-938. https://doi.org/10.1038/ng.3355
Hobbs, Ryan P. ; Depianto, Daryle J. ; Jacob, Justin T. ; Han, Minerva C. ; Chung, Byung Min ; Batazzi, Adriana S. ; Poll, Brian G. ; Guo, Yajuan ; Han, Jingnan ; Ong, Sufey ; Zheng, Wenxin ; Taube, Janis M ; Cihakova, Daniela ; Wan, Fengyi ; Coulombe, Pierre A. / Keratin-dependent regulation of Aire and gene expression in skin tumor keratinocytes. In: Nature Genetics. 2015 ; Vol. 47, No. 8. pp. 933-938.
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