The SLE-associated Pbx1-d isoform acts as a dominant-negative transcriptional regulator

M. Sengupta, S. Liang, H. H.S. Potula, L. J. Chang, L. Morel

Resultado de la investigación: Articlerevisión exhaustiva

6 Citas (Scopus)


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.

Idioma originalEnglish (US)
Páginas (desde-hasta)653-657
Número de páginas5
PublicaciónGenes and Immunity
EstadoPublished - dic. 2012
Publicado de forma externa

ASJC Scopus subject areas

  • Immunology
  • Genetics
  • Genetics(clinical)


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