The Drosophila F box protein archipelago regulates dMyc protein levels in vivo.
BACKGROUND
The Myc oncoprotein is an important regulator of cellular growth in metazoan organisms. Its levels and activity are tightly controlled in vivo by a variety of mechanisms. In normal cells, Myc protein is rapidly degraded, but the mechanism of its degradation is not well understood.


RESULTS
Here we present genetic and biochemical evidence that Archipelago (Ago), the F box component of an SCF-ubiquitin ligase and the Drosophila ortholog of a human tumor suppressor, negatively regulates the levels and activity of Drosophila Myc (dMyc) protein in vivo. Mutations in archipelago (ago) result in strongly elevated dMyc protein levels and increased tissue growth. Genetic interactions indicate that ago antagonizes dMyc function during development. Archipelago binds dMyc and regulates its stability, and the ability of Ago to bind dMyc in vitro correlates with its ability to inhibit dMyc accumulation in vivo.


CONCLUSIONS
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.
Moberg
Kenneth H
KH
Massachusetts General Hospital Cancer Center, Building 149, 13th Street, Charlestown, MA 02129 USA. kmoberg@cellbio.emory.edu
Mukherjee
Ashim
A
Veraksa
Alexey
A
Artavanis-Tsakonas
Spyros
S
Hariharan
Iswar K
IK
D000595:Amino Acid Sequence; D000818:Animals; D015152:Blotting, Northern; D001837:Body Weights and Measures; D002453:Cell Cycle / Q000502:physiology*; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004330:Drosophila; D029721:Drosophila Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D044783:F-Box Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D005434:Flow Cytometry; D007150:Immunohistochemistry; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D011233:Precipitin Tests; D034622:RNA Interference; D016415:Sequence Alignment; D014157:Transcription Factors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014162:Transfection; D014921:Wings, Animal / Q000166:cytology
D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D044783:F-Box Proteins; C102284:Myc protein, Drosophila; D014157:Transcription Factors; C488876:ago protein, Drosophila