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A Higher-Order Complex Containing AF4 and ENL Family Proteins with P-TEFb Facilitates Oncogenic and Physiologic MLL-Dependent Transcription
Open accessAbstract
Summary AF4 and ENL family proteins are frequently fused with MLL, and comprise a higher order complex (designated AEP) containing the P-TEFb transcription elongation factor. Here, we show that AEP is normally recruited to MLL-target chromatin to facilitate transcription. By contrast, MLL oncoproteins fused with AEP components constitutively form MLL/AEP hybrid complexes to cause sustained target gene expression, which leads to transformation of hematopoietic progenitors. Furthermore, MLL-AF6, an MLL fusion with a cytoplasmic protein, does not form such hybrid complexes, but nevertheless constitutively recruits AEP to target chromatin via unknown alternative mechanisms. Thus, AEP recruitment is an integral part of both physiological and pathological MLL-dependent transcriptional pathways. Bypass of its normal recruitment mechanisms is the strategy most frequently employed by MLL oncoproteins.
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Dull, T., Zufferey, R., Kelly, M., Mandel, R. J., Nguyen, M., Trono, D., & Naldini, L. (1998) · Journal of Virology · doi:10.1128/jvi.72.11.8463-8471.1998 · Cited by 3,341
Chemically ubiquitylated histone H2B stimulates hDot1L-mediated intranucleosomal methylation
McGinty, R. K., Kim, J., Chatterjee, C., Roeder, R. G., & Muir, T. W. (2008) · Nature · doi:10.1038/nature06906 · Cited by 563
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Shilatifard, A. (2012) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-051710-134100 · Cited by 1,091
Potent inhibition of DOT1L as treatment of MLL-fusion leukemia
Daigle, S. R., Olhava, E. J., Therkelsen, C. A., Basavapathruni, A., Jin, L., Boriack-Sjodin, P. A., Allain, C. J., Klaus, C. R., Raimondi, A., Scott, M. P., et al. (2013) · Blood · doi:10.1182/blood-2013-04-497644 · Cited by 722
The histone demethylase KDM1A sustains the oncogenic potential of MLL-AF9 leukemia stem cells
Harris, W. J., Huang, X., Lynch, J. T., Spencer, G. J., Hitchin, J. R., Li, Y., Ciceri, F., Blaser, J. G., Greystoke, B. F., Jordan, A. M., et al. (2012) · Cancer Cell · doi:10.1016/j.ccr.2012.03.014 · Cited by 566
Epigenetic balance of gene expression by Polycomb and COMPASS families
Piunti, A., & Shilatifard, A. (2016) · Science · doi:10.1126/science.aad9780 · Cited by 524
Menin-MLL inhibitors reverse oncogenic activity of MLL fusion proteins in leukemia
Grembecka, J., He, S., Shi, A., Purohit, T., Muntean, A. G., Sorenson, R. J., Showalter, H. D., Murai, M. J., Belcher, A. M., Hartley, T., et al. (2012) · Nature Chemical Biology · doi:10.1038/nchembio.773 · Cited by 462
Metadata
- Authors
- Yokoyama, A., Lin, M., Naresh, A., Kitabayashi, I., & Cleary, M. L.
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2010-02
- Volume
- 17
- Issue
- 2
- Pages
- 198-212
- ISSN
- 1535-6108 (ISSN-L)
- OpenAlex
- W2073652391
- Cited by
- 374
- References
- 2
- FWCI
- 11.81
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Yokoyama, A., Lin, M., Naresh, A., Kitabayashi, I., & Cleary, M. L. (2010). A Higher-Order Complex Containing AF4 and ENL Family Proteins with P-TEFb Facilitates Oncogenic and Physiologic MLL-Dependent Transcription. Cancer Cell. https://doi.org/10.1016/j.ccr.2009.12.040
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