High impact information on slmb

• Role for Slimb in the degradation of Drosophila Period protein phosphorylated by Doubletime [1].
• Loss of function of slimb results in a cell-autonomous accumulation of high levels of both Ci and Arm, and the ectopic expression of both Hh- and Wg- responsive genes [2].
• Here we describe a new gene, slimb (for supernumerary limbs), which negatively regulates both of these signal transduction pathways [2].
• By analyzing slmb germline clones, we found that loss of Slmb provoked a reduction in E2f2 and Dp levels, which correlated with misregulation of mitotic cycles during cyst formation, abnormal nurse cell endoreplication and impairment of dumping of the nurse cell content into the oocyte [3].
• We observed that in slmb somatic clones, morphogenesis of the germarium and encapsulation of the cyst were altered, giving rise to egg chambers with extra germline cells and two oocytes [3].

Biological context of slmb

• We have investigated the fate of slmb(-) clones, which disappear before adulthood, and found that two mechanisms of cell elimination can account for imaginal cell regeneration: an early apoptosis and a mechanism of sorting-out which excludes all slmb(-) clones from all imaginal discs [4].
• We analyzed its participation in egg chamber development and found that slmb is required in both the follicle cells and the germline at different stages of oogenesis [3].
• Indeed, ectopic expression of a dad-LacZ enhancer trap revealed that the Dpp pathway was upregulated in slmb somatic clones and, consistent with this, ectopic accumulation of the co-Smad protein, Medea, was recorded [3].
• Furthermore, in slmb somatic clones, we observed ectopic Fasciclin 3 expression, suggesting a delay in follicle cell differentiation, which correlated with the occurrence of ectopic polar cells, lack of interfollicular stalks and mislocalization of the oocyte [3].
• Slimb (Slmb) is a Drosophila F-Box protein that fulfills several roles in development and cell physiology [3].

Anatomical context of slmb

• Here, we report that Slimb, an F-box protein that targets proteins to the SCFcomplex [14,15], plays a role in limiting centrosome replication [5].
• In cultured cells, inhibition of SkpA and Slimb via RNAi increases levels of both the full-length Relish protein and the processed Rel-homology domain [6].

Physical interactions of slmb

• CKI phosphorylation of Ci confers binding to the F-box protein Slimb/beta-TRCP, the substrate recognition component of the SCF(Slimb/beta-TRCP) ubiquitin ligase required for Ci processing [7].

Other interactions of slmb

• We show here that in leg discs, lack of slmb function derepresses the transcription of wg independently of Hh signaling [4].
• Strong evidence indicates that this dpp modification can be linked to imaginal disc regeneration following slmb(-) cell elimination [4].
• Drosophila Slimb (Slmb) is a F-box/WD40 protein which potentially participates in the ubiquitin proteolysis machinery [4].
• We also explore the phosphorylated motifs in Ci that are recognized by Slimb and provide some evidence that silencing of Ci-155 by phosphorylation may involve more than binding to Slimb [8].
• We propose that phosphorylation of Ci by CKI creates multiple Slimb/beta-TRCP binding sites that act cooperatively to recruit SCF(Slimb/beta-TRCP) [7].

References