Delta
Precise
regulation of Notch signaling activity is critical for development of many
different tissues. Here, we show that the zebrafish insertional mutation Hi904 attenuates Notch signaling, and
is allelic to mind bomb. We show that Mind bomb protein displays E3 ubiquitin ligase activity in
vitro and that it is associated with Delta and enhances
its ubiquitination and internalization in transfected cells. Furthermore, by functional analysis of
three conserved regions of Mind bomb, we show that the N-terminal half is
required for Delta association, the ankyrin repeats
are important for Delta internalization, and the ring fingers are required for
Delta ubiquitination. Thus, the three functionally
distinct modules of Mind bomb work cooperatively to regulate Notch signaling by
associating with, ubiquitinating, and internalizing
Delta.
PMID: 15013799 [PubMed - in process]