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- Title
The SLE-associated Pbx1-d isoform acts as a dominant-negative transcriptional regulator.
- Authors
Sengupta, M; Liang, S; Potula, H-H S; Chang, L-J; Morel, L
- Abstract
Pbx1 is a transcription factor involved in multiple cellular processes, including the maintenance of self-renewal of hematopoietic progenitors. We have shown that the CD4+ T-cell expression of a novel splice isoform of Pbx1, Pbx1-d, is associated with lupus susceptibility in the NZM2410 mouse and in lupus patients. The function of Pbx1 in T cells is unknown, but the splicing out of the DNA-binding domain in Pbx1-d predicts a dominant-negative function. In support of this hypothesis, we have shown that Pbx1-d transduction accelerates differentiation of MC3T3-E1 osteoblast pregenitors and mimics the effect of short hairpin RNA silencing of Pbx1. Conversely, Pbx1-d transduction reduced the expression of Sox3, a gene strongly transactivated by Pbx1, and Pbx1-d did not bind the Sox3 promoter. These results constitute a first step towards the understanding on how Pbx1-d contributes to systemic autoimmunity in the NZM2410 mouse model as well as in lupus patients.
- Subjects
TRANSCRIPTION factors; GENETIC regulation; HEMATOPOIETIC stem cells; GENE expression; CD4 antigen; LUPUS erythematosus; LABORATORY mice; CELL differentiation; DNA-binding proteins
- Publication
Genes & Immunity, 2012, Vol 13, Issue 8, p653
- ISSN
1466-4879
- Publication type
Article
- DOI
10.1038/gene.2012.43