The Drosophila F Box Protein Archipelago Regulates dMyc Protein Levels In Vivo

Abstract

Our data indicate that archipelago is an important inhibitor of dMyc in developing tissues. Because archipelago can also regulate Cyclin E levels and Notch activity, these results indicate how a single F box protein can be responsible for the degradation of key components of multiple pathways that control growth and cell cycle progression.

Fbw7 regulates the activity of endoreduplication mediators and the p53 pathway to prevent drug-induced polyploidy

“…This finding explains the frequently elevated expression of cyclin E in breast tumors lacking active Fbw7 (Ekholm-Reed et al, 2004). Other substrates include the oncoproteins c-Myc (Moberg et al, 2004;Welcker et al, 2004;Yada et al, 2004), c-Jun (Nateri et al, 2004;Wei et al, 2005) and Notch (Gupta-Rossi et al, 2001;Oberg et al, 2001;Wu et al, 2001), all of which act to increase cell volume, proliferation and de-differentiation. In addition, Aurora A kinase, an important regulator of mitosis that is frequently overexpressed in human cancer tissues, also serves as a substrate of Fbw7 (Mao et al, 2004;Fujii et al, 2006).…”

Myc in model organisms: A view from the flyroom

“…Interestingly, although the hypomorphic mutant flies are smaller than normal they appear normally proportioned ( Fig. 1) [19,20]. Many of these same defects are characteristic of flies with growth deficits, and also appear in flies with mutations in genes encoding ribosomal proteins (the Minute class of mutations) and other components of ribosome biogenesis.…”

“…Similar competitive outcomes result from other manipulations that allow some cells to have higher dMyc levels than their neighbors. For example, loss of archipelago (ago), which encodes a Drosophila F box protein homologous to human Fbw7, results in elevated dMyc protein levels and a competitive advantage that allows ago mutant cells to overtake whole body structures while wildtype cells are eliminated [20]. Also, overexpression of the dMyc antagonist dMnt slows growth of cell clones, and these cells are eventually eliminated [8].…”

Expanding the Iroquois genes repertoire: a non-transcriptional function in cell cycle progression

“…In addition to the previously described transcriptional mechanisms that regulate the expression of the Iro genes, 7,14,[28][29][30][31][32][33][34][35][36] we now propose that there should also exist post-transcriptional mechanisms to ensure an efficient control of the levels of Iro proteins. In this context, it is of interest that we have indications that depletion of the F-box protein Archipelago (Ago), which induces the degradation through the proteasome pathway of the cell proliferation-promoting proteins CycE and Myc, 37,38 stabilizes exogenously provided Caup (Figs. 2C-E).…”