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Molecular and Cellular Biology, September 2005, p. 7900-7916, Vol. 25, No. 17
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.17.7900-7916.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Regulation of RelB Expression during the Initiation of Dendritic Cell Differentiation

Pedro J. Cejas,1 Louise M. Carlson,1 Despina Kolonias,1 Jian Zhang,1 Inna Lindner,1 Daniel D. Billadeau,2 Lawrence H. Boise,1 and Kelvin P. Lee1*

University of Miami School of Medicine, Department of Microbiology and Immunology, Miami, Florida 33136,1 Mayo Clinic, Oncology Research, Rochester, Minnesota 559052

Received 13 March 2005/ Returned for modification 14 April 2005/ Accepted 8 June 2005

The transcription factor RelB is required for proper development and function of dendritic cells (DCs), and its expression is upregulated early during differentiation from a variety of progenitors. We explored this mechanism of upregulation in the KG1 cell line model of a DC progenitor and in the differentiation-resistant KG1a subline. RelB expression is relatively higher in untreated KG1a cells but is upregulated only during differentiation of KG1 by an early enhancement of transcriptional elongation, followed by an increase in transcription initiation. Restoration of protein kinase CßII (PKCßII) expression in KG1a cells allows them to differentiate into DCs. We show that PKCßII also downregulated constitutive expression of NF-{kappa}B in KG1a-transfected cells and restores the upregulation of RelB during differentiation by increased transcriptional initiation and elongation. The two mechanisms are independent and sensitive to PKC signaling levels. Conversely, RelB upregulation was inhibited in primary human monocytes where PKCßII expression was knocked down by small interfering RNA targeting. Altogether, the data show that RelB expression during DC differentiation is controlled by PKCßII-mediated regulation of transcriptional initiation and elongation.

* Corresponding author. Mailing address: University of Miami School of Medicine, Department of Microbiology and Immunology, Papanicolaou Bldg. Room 211, 1550 NW 10th Ave., Miami, FL 33136. Phone: (305) 243-1044. Fax: (305) 243-4409. E-mail: klee{at}med.miami.edu.

Molecular and Cellular Biology, September 2005, p. 7900-7916, Vol. 25, No. 17
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.17.7900-7916.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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