Dominant-negative mutation in the beta 2 and beta 6 proteasome subunit genes affect alternative cell fate decisions in the Drosophila sense organ lineage

In Drosophila, dominant-negative mutations in the beta 2 and beta 6 proteas ome catalytic subunit genes have been identified as dominant temperature-se nsitive (DTS) mutations. At restrictive temperature, beta 2 and beta 6 DTS mutations confer lethality at the pupal stage. I investigate here the role of proteasome activity in regulating cell fate decisions in the sense organ lineage at the early pupal stage. Temperature shift experiments in beta 2 and beta 6 DTS mutant pupae occasionally resulted in external sense organs with two sockets and no shaft. This double-socket phenotype was strongly en hanced in conditions in which Notch signaling was up-regulated. Furthermore , conditional overexpression of the beta 6 dominant-negative mutant subunit led to shaft to socket and to neuron-to-sheath cell fate transformations, which are both usually associated with increased Notch signaling activity. Finally, expression of the beta 6 dominant negative mutant subunit led to t he stabilization of an ectopically expressed nuclear form of Notch in imagi nal wing discs. This study demonstrates that mutations affecting two distin ct proteasome catalytic subunits affect two alternative cell fate decisions and enhance Notch signaling activity in the sense organ lineage. These fin dings raise the possibility that the proteasome targets an active form of t he Notch receptor for degradation in Drosophila.