Ligand-induced cleavage and regulation of nuclear entry of Notch in Drosophila melanogaster embryos

Notchic-ER chimeras display hormone-dependent transformation, nuclear accumulation, phosphorylation and CBF1 activation

“…Therefore, we conclude that the phosphorylation induced by hormone activation of Notch ic -ER chimeras occurs on the Notch ic sequence present in the fusion protein. In support of our data, phosphorylation of Notch has been previously described in Drosophila (Kidd et al, 1989(Kidd et al, , 1998.…”

“…The engagement of ligand somehow induces proteolytic processing that releases the intracellular portion of the receptor (N ic ) from the plasma membrane. Once free from the membrane, it is thought that N ic translocates to the nucleus where it interacts with e ector molecules to alter gene expression (Ahmad et al, 1995;Fehon et al, 1991;Fortini et al, 1993;Jariault et al, 1995;Kidd et al, 1998;Kopan et al, 1996;Lieber et al, 1993;Schroeter et al, 1998;Struhl and Adachi, 1998;Zagouras et al, 1995). One such e ector molecule is CBF1, a transcriptional regulatory protein that functions as a repressor in the absence of activated Notch.…”

“…Although certain aspects of this model are compelling, there is considerable debate on the physiological role of nuclear Notch proteins. Most of the data providing evidence for nuclear function comes from ectopic expression of engineered N ic proteins in both vertebrate and invertebrate cell culture systems (Capobianco et al, 1997;Fortini et al, 1993;Kidd et al, 1998;Kopan et al, 1996;Lecourtois and Schweisguth, 1998;Lieber et al, 1993;Rebay et al, 1993;Schroeter et al, 1998;Struhl and Adachi, 1998). However, a strict correlation of ligand-induced nuclear localization and Notch function remains elusive.…”

Notch signaling patternsDrosophilamesodermal segments by regulating the bHLH transcription factortwist

“…Females carrying twist-GAL4 on both the X and the second chromosomes {2X twist-GAL4} (Baylies et al, 1995) were crossed to males carrying constitutively active forms of Notch or Su(H): UAS-N intra (Lieber et al, 1993) or UAS-Su(H)-VP16 (Kidd et al, 1998). N intra encodes the intracellular domain of Notch (N icd ) that is released upon Notch cleavage.…”

“…Su(H) binds specific enhancer sequences, recruits co-repressors, such as Hairless, and represses transcription Furriols and Bray, 2000;Klein et al, 2000;Morel et al, 2001). Upon ligand binding, the Notch intracellular domain, N icd , is released from the cell membrane and translocates into the nucleus (Kidd et al, 1998;Struhl and Adachi, 1998). N icd then associates with Su(H) and alleviates Su(H)-mediated repression, for example by displacing corepressors.…”