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The PAF Complex Synergizes with MLL Fusion Proteins at HOX Loci to Promote Leukemogenesis
Open accessAbstract
Summary MLL is involved in chromosomal rearrangements that generate fusion proteins with deregulated transcriptional activity. The mechanisms of MLL fusion protein-mediated transcriptional activation are poorly understood. Here we show MLL interacts directly with the Polymerase Associated Factor complex (PAFc) through sequences flanking the CxxC domain. PAFc interacts with RNA polymerase II and stimulates post-translational histone modifications. PAFc augments MLL and MLL-AF9 mediated transcriptional activation of Hoxa9. Conversely, knock down of PAFc disrupts MLL fusion protein-mediated transcriptional activation and MLL recruitment to target loci. PAFc gene expression is down regulated during hematopoiesis and likely serves to regulate MLL function. Deletions of MLL that abolish interactions with PAFc also eliminate MLL-AF9 mediated immortalization indicating an essential function for this interaction in leukemogenesis.
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Metadata
- Authors
- Muntean, A. G., Tan, J., Sitwala, K., Huang, Y., Bronstein, J., Connelly, J. A., Basrur, V., Elenitoba-Johnson, K. S. J., & Hess, J. L.
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2010-06
- Volume
- 17
- Issue
- 6
- Pages
- 609-621
- ISSN
- 1535-6108 (ISSN-L)
- OpenAlex
- W2110726136
- Cited by
- 231
- References
- 0
- FWCI
- 8.15
- Type
- journal article
- Language
- en
- Open access
- bronze
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- CoChat. (2026). Citation check: The PAF Complex Synergizes with MLL Fusion Proteins at HOX Loci to Promote Leukemogenesis. https://app.cochat.ai/papers/10.1016/j.ccr.2010.04.012
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- Muntean, A. G., Tan, J., Sitwala, K., Huang, Y., Bronstein, J., Connelly, J. A., Basrur, V., Elenitoba-Johnson, K. S. J., & Hess, J. L. (2010). The PAF Complex Synergizes with MLL Fusion Proteins at HOX Loci to Promote Leukemogenesis. Cancer Cell. https://doi.org/10.1016/j.ccr.2010.04.012
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