Abstract
The Drosophila Myb protein, DMyb, is a transcription factor important for cell proliferation and development. Unlike the mRNAs produced by mammalian myb genes, Drosophila myb transcripts do not fluctuate substantially during the cell cycle. A comprehensive analysis of the localization and degradation of the DMyb protein has now revealed that DMyb is present in nuclei during S phase of all mitotically active tissues throughout embryogenesis and larval development. However, DMyb and Mip130, another member of the Myb complex, are not uniformly distributed throughout the nucleus. Instead, both proteins, which colocalize, appear to be specifically excluded from heterochromatic regions of chromosomes. Furthermore, DMyb and Mip130 are unstable proteins that are degraded during prometaphase of mitosis. The timing of their degradation is reminiscent of Cyclin A, but at least for DMyb, the mechanism differs; although DMyb degradation is dependent on core APC/C components, it does not depend on the Fizzy or Fizzy-related adaptor proteins. DMyb levels are also high in actively endoreplicating polyploid cells, but there is no indication of cyclical degradation. We conclude that cell cycle specific degradation of DMyb and Mip130 is likely to be utilized as a key regulatory mechanism in down-regulating their levels and the activity of the Myb complex.
Original language | English (US) |
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Pages (from-to) | 646-661 |
Number of pages | 16 |
Journal | Mechanisms of Development |
Volume | 125 |
Issue number | 7 |
DOIs | |
State | Published - Jul 2008 |
Externally published | Yes |
Bibliographical note
Funding Information:We thank M. Botchan, J. Lipsick, and F. Sprenger for generously supplying us with fly stocks and antibodies; the Bloomington Stock Center for providing Drosophila strains; and M. Rovani, J. McEllin, F. Thompson, and M. Frolov for useful discussions and ideas. The A12 and C1A9 monoclonal antibodies developed by C.F. Lehner and L.L. Wallrath were obtained from the Developmental Studies Hybridoma Bank developed under the auspices of the NICHD and maintained by The University of Iowa, Department of Biological Sciences, Iowa City, IA 52242. Work reported here was supported by a National Institutes of Health Grant to A.L.K. (GM68961).
Keywords
- APC/C
- Cell cycle
- DMyb
- Dm myb
- Drosophila
- Mitosis
- Myb
- Myb complex
- Proto-oncogene