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.
Original language | English (US) |
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Pages (from-to) | 653-657 |
Number of pages | 5 |
Journal | Genes and Immunity |
Volume | 13 |
Issue number | 8 |
DOIs | |
State | Published - Dec 2012 |
Externally published | Yes |
Keywords
- Lupus
- Pbx1
- T cells
ASJC Scopus subject areas
- Immunology
- Genetics
- Genetics(clinical)