Journal article
Animal-specific C-terminal domain links myeloblastosis oncoprotein (Myb) to an ancient repressor complex
Proceedings of the National Academy of Sciences - PNAS, Vol.108(42), pp.17438-17443
10/18/2011
DOI: 10.1073/pnas.1111855108
PMCID: PMC3198365
PMID: 21969598
Abstract
Members of the Myb oncoprotein and E2F-Rb tumor suppressor protein families are present within the same highly conserved multiprotein transcriptional repressor complex, named either as Myb and synthetic multivuval class B (Myb-MuvB) or as
Drosophila
Rb E2F and Myb-interacting proteins (dREAM). We now report that the animal-specific C terminus of
Drosophila
Myb but not the more highly conserved N-terminal DNA-binding domain is necessary and sufficient for (
i
) adult viability, (
ii
) proper localization to chromosomes in vivo, (
iii
) regulation of gene expression in vivo, and (
iv
) interaction with the highly conserved core of the MuvB/dREAM transcriptional repressor complex. In addition, we have identified a conserved peptide motif that is required for this interaction. Our results imply that an ancient function of Myb in regulating G2/M genes in both plants and animals appears to have been transferred from the DNA-binding domain to the animal-specific C-terminal domain. Increased expression of
B-MYB/MYBL2
, the human ortholog of
Drosophila Myb
, correlates with poor prognosis in human patients with breast cancer. Therefore, our results imply that the specific interaction of the C terminus of Myb with the MuvB/dREAM core complex may provide an attractive target for the development of cancer therapeutics.
Details
- Title: Subtitle
- Animal-specific C-terminal domain links myeloblastosis oncoprotein (Myb) to an ancient repressor complex
- Creators
- Laura Andrejka - Stanford UniversityHong Wen - University of Texas M. D. Anderson Cancer CenterJonathan Ashton - Stanford UniversityMegan Grant - Stanford UniversityKevin Iori - Stanford UniversityAmy Wang - Stanford UniversityJ. Robert Manak - University of IowaJoseph S Lipsick - Stanford University
- Resource Type
- Journal article
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, Vol.108(42), pp.17438-17443
- DOI
- 10.1073/pnas.1111855108
- PMID
- 21969598
- PMCID
- PMC3198365
- NLM abbreviation
- Proc Natl Acad Sci U S A
- ISSN
- 0027-8424
- eISSN
- 1091-6490
- Publisher
- National Academy of Sciences
- Language
- English
- Date published
- 10/18/2011
- Academic Unit
- Stead Family Department of Pediatrics; Biology; Craniofacial Anomalies Research Center
- Record Identifier
- 9984217412802771
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