Notch3 and the Notch3-upregulated RNA-binding protein HuD regulate Ikaros alternative splicing.

ABSTRACT: Constitutive activation of the transmembrane receptor, Notch3, and loss of function of the hematopoietic transcription repressor, Ikaros (IK), play direct roles in T-cell differentiation and leukemogenesis that are dependent on pre-T-cell receptor (pre-TCR) signaling. We demonstrate the occurrence of crosstalk between Notch3 and IK that results in transcriptional regulation of the gene encoding the pTalpha chain of the pre-TCR. We also show that, in the presence of the pre-TCR, constitutive activation of Notch3 in thymocytes causes increased expression of dominantnegative non-DNA-binding IK isoforms, which are able to restrain the IK inhibition of Notch3's transcriptional activation of pTalpha. This effect appears to be mediated by Notch3's pre-TCR-dependent upregulation of the RNA-binding

SUBMITTER: Bellavia D 

PROVIDER: S-EPMC1829386 | biostudies-literature | 2007 Mar

REPOSITORIES: biostudies-literature