Distinct expression and function of alternatively spliced Tbx5 isoforms in cell growth and differentiation.

ABSTRACT: Mutations in the T-box transcription factor Tbx5 cause Holt-Oram syndrome, an autosomal dominant disease characterized by a wide spectrum of cardiac and upper limb defects with variable expressivity. Tbx5 haploinsufficiency has been suggested to be the underlying mechanism, and experimental models are consistent with a dosage-sensitive requirement for Tbx5 in heart development. Here, we report that Tbx5 levels are regulated through alternative splicing that generates, in addition to the known 518-amino-acid protein, a C-terminal truncated isoform. This shorter isoform retains the capacity to bind DNA, but its interaction with Tbx5 collaborators such as GATA-4 is altered. In vivo, the two spliced isoforms are oppositely regulated in a temporal and growth factor-dependent manner and are pres

SUBMITTER: Georges R 

PROVIDER: S-EPMC2423137 | biostudies-literature | 2008 Jun

REPOSITORIES: biostudies-literature