Abstract
Acute leukemias induced by MLL chimeric oncoproteins are among the subset of cancers distinguished by a paradoxical dependence on GSK-3 kinase activity for sustained proliferation. We demonstrate here that GSK-3 maintains the MLL leukemia stem cell transcriptional program by promoting the conditional association of CREB and its coactivators TORC and CBP with homedomain protein MEIS1, a critical component of the MLL-subordinate program, which in turn facilitates HOX-mediated transcription and transformation. This mechanism also applies to hematopoietic cells transformed by other HOX genes, including CDX2, which is highly expressed in a majority of acute myeloid leukemias, thus providing a molecular approach based on GSK-3 inhibitory strategies to target HOX-associated transcription in a broad spectrum of leukemias.
| Original language | English |
|---|---|
| Pages (from-to) | 597-608 |
| Number of pages | 12 |
| Journal | Cancer Cell |
| Volume | 17 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - Jun 15 2010 |
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Keywords
- CELLCYCLE
ASJC Scopus subject areas
- Cancer Research
- Cell Biology
- Oncology
Cite this
GSK-3 Promotes Conditional Association of CREB and Its Coactivators with MEIS1 to Facilitate HOX-Mediated Transcription and Oncogenesis. / Wang, Zhong; Iwasaki, Masayuki; Ficara, Francesca; Lin, Chenwei; Matheny, Christina; Wong, Stephen H K; Smith, Kevin S.; Cleary, Michael L.
In: Cancer Cell, Vol. 17, No. 6, 15.06.2010, p. 597-608.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - GSK-3 Promotes Conditional Association of CREB and Its Coactivators with MEIS1 to Facilitate HOX-Mediated Transcription and Oncogenesis
AU - Wang, Zhong
AU - Iwasaki, Masayuki
AU - Ficara, Francesca
AU - Lin, Chenwei
AU - Matheny, Christina
AU - Wong, Stephen H K
AU - Smith, Kevin S.
AU - Cleary, Michael L.
PY - 2010/6/15
Y1 - 2010/6/15
N2 - Acute leukemias induced by MLL chimeric oncoproteins are among the subset of cancers distinguished by a paradoxical dependence on GSK-3 kinase activity for sustained proliferation. We demonstrate here that GSK-3 maintains the MLL leukemia stem cell transcriptional program by promoting the conditional association of CREB and its coactivators TORC and CBP with homedomain protein MEIS1, a critical component of the MLL-subordinate program, which in turn facilitates HOX-mediated transcription and transformation. This mechanism also applies to hematopoietic cells transformed by other HOX genes, including CDX2, which is highly expressed in a majority of acute myeloid leukemias, thus providing a molecular approach based on GSK-3 inhibitory strategies to target HOX-associated transcription in a broad spectrum of leukemias.
AB - Acute leukemias induced by MLL chimeric oncoproteins are among the subset of cancers distinguished by a paradoxical dependence on GSK-3 kinase activity for sustained proliferation. We demonstrate here that GSK-3 maintains the MLL leukemia stem cell transcriptional program by promoting the conditional association of CREB and its coactivators TORC and CBP with homedomain protein MEIS1, a critical component of the MLL-subordinate program, which in turn facilitates HOX-mediated transcription and transformation. This mechanism also applies to hematopoietic cells transformed by other HOX genes, including CDX2, which is highly expressed in a majority of acute myeloid leukemias, thus providing a molecular approach based on GSK-3 inhibitory strategies to target HOX-associated transcription in a broad spectrum of leukemias.
KW - CELLCYCLE
UR - http://www.scopus.com/inward/record.url?scp=77953233857&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77953233857&partnerID=8YFLogxK
U2 - 10.1016/j.ccr.2010.04.024
DO - 10.1016/j.ccr.2010.04.024
M3 - Article
C2 - 20541704
AN - SCOPUS:77953233857
VL - 17
SP - 597
EP - 608
JO - Cancer Cell
JF - Cancer Cell
SN - 1535-6108
IS - 6
ER -