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Title: PEBP2-2/CBF-2 dependent phosphorylation of RUNX1 and p300 by HIPK2: Implications for leukemogenesis
Authors: Wee, H.-J.
Voon, D.C.-C.
Bae, S.-C.
Ito, Y. 
Issue Date: 1-Nov-2008
Citation: Wee, H.-J., Voon, D.C.-C., Bae, S.-C., Ito, Y. (2008-11-01). PEBP2-2/CBF-2 dependent phosphorylation of RUNX1 and p300 by HIPK2: Implications for leukemogenesis. Blood 112 (9) : 3777-3787. ScholarBank@NUS Repository.
Abstract: The heterodimeric transcription factor RUNX1/PEBP2-β (also known as AML1/CBF-β) is essential for definitive hematopoiesis. Here, we show that interaction with PEBP2-β leads to the phosphorylation of RUNX1, which in turn induces p300 phosphorylation. This is mediated by homeodomain interacting kinase 2 (HIPK2), targeting Ser249, Ser273, and Thr 276 in RUNX1, in a mannerthat is also dependent on the RUNX1 PY motif. Importantly, we observed the in vitro disruption of this phosphorylation cascade by multiple leukemogenic genetic defects targeting RUNX1/CBFB. In particular, the oncogenic protein PEBP2-β-SMMHC prevents RUNX1/p300 phosphorylation by sequestering HIPK2 to mlslocalized RUNX1/β-SMMHC complexes. Therefore, phosphorylation of RUNX1 appears a critical step In Its association with and phosphorylation of p300, and Its disruption may be a common theme In RUASX1-associated leukemogenesls. © 2008 by The American Society of Hematology.
Source Title: Blood
ISSN: 00064971
DOI: 10.1182/blood-2008-01-134122
Appears in Collections:Staff Publications

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