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First published online 12 December 2006
doi: 10.1242/jcs.03317

Journal of Cell Science 120, 125-136 (2007)
Published by The Company of Biologists 2007
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Research Article

Sumoylation dynamics during keratinocyte differentiation

Adeline F. Deyrieux1, Germán Rosas-Acosta1, Michelle A. Ozbun2 and Van G. Wilson1,*

1 Department of Molecular and Microbial Pathogenesis, College of Medicine, Texas A&M Health Science Center, College Station, TX 77843-1114, USA
2 Department of Molecular Genetics and Microbiology, and of Obstetrics and Gynecology, University of New Mexico School of Medicine, 915 Camino de Salud NE, Cancer Research Facility (CRF) 303, Albuquerque, NM 87131, USA

* Author for correspondence (e-mail: wilson{at}medicine.tamhsc.edu)

Accepted 25 October 2006

SUMO modification regulates the activity of numerous transcription factors that have a direct role in cell-cycle progression, apoptosis, cellular proliferation, and development, but its role in differentiation processes is less clear. Keratinocyte differentiation requires the coordinated activation of a series of transcription factors, and as several crucial keratinocyte transcription factors are known to be SUMO substrates, we investigated the role of sumoylation in keratinocyte differentiation. In a human keratinocyte cell line model (HaCaT cells), Ca2+-induced differentiation led to the transient and coordinated transcriptional activation of the genes encoding crucial sumoylation system components, including SAE1, SAE2, Ubc9, SENP1, Miz-1 (PIASxß), SUMO2 and SUMO3. The increased gene expression resulted in higher levels of the respective proteins and changes in the pattern of sumoylated substrate proteins during the differentiation process. Similarly to the HaCaT results, stratified human foreskin keratinocytes showed an upregulation of Ubc9 in the suprabasal layers. Abrogation of sumoylation by Gam1 expression severely disrupted normal HaCaT differentiation, consistent with an important role for sumoylation in the proper progression of this biological process.

Key words: Keratinocyte, Differentiation, SUMO, HaCaT, Ubc9




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