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MOZ-TIF2-induced acute myeloid leukemia requires the MOZ nucleosome binding motif and TIF2-mediated recruitment of CBP

MOZ-TIF2-induced acute myeloid leukemia requires the MOZ nucleosome binding motif and TIF2-mediated recruitment of CBP
MOZ-TIF2-induced acute myeloid leukemia requires the MOZ nucleosome binding motif and TIF2-mediated recruitment of CBP
The MOZ-TIF2 fusion is associated with acute myeloid leukemia (AML) with inv(8)(p11q13). MOZ is a MYST family histone acetyltransferase (HAT), whereas TIF2 is a nuclear receptor coactivator that associates with CREB binding protein (CBP). Here we demonstrate that MOZ-TIF2 has transforming properties in vitro and causes AML in a murine bone marrow transplant assay. The C2HC nucleosome recognition motif of MOZ is essential for transformation, whereas MOZ HAT activity is dispensable. However, MOZ-TIF2 interaction with CBP through the TIF2 CBP interaction domain (CID) is essential for transformation. These results indicate that nucleosomal targeting by MOZ and recruitment of CBP by TIF2 are critical requirements for MOZ-TIF2 transformation and indicate that MOZ gain of function contributes to leukemogenesis.
1535-6108
259-271
Deguchi, Kenji
54222618-8273-4481-b902-ec24e881d8b9
Ayton, Paul M.
960f4b33-3dd1-4930-b902-5ecca3bc7476
Carapeti, Melina
c4685545-f43e-4ca7-9d8c-a790ef5f19fb
Kutok, Jeffery L.
50ee3dc0-d546-40d0-b133-76e5dea66dbe
Snyder, Cynthia S.
01192f77-1b81-4dd0-9995-4f980ea60f4a
Williams, Ifor R.
1740a596-2ec2-4669-9171-71da0b3b7f8e
Cross, Nicholas C.P.
f87650da-b908-4a34-b31b-d62c5f186fe4
Glass, Christopher K.
07c62fbf-c032-493d-95e4-50658313ed31
Cleary, Michael L.
eddf3827-008f-451c-8de9-fb398d919d1a
Gilliland, D. Gary
eb6d954f-0e6e-411b-ac75-7c7dab6de745
Deguchi, Kenji
54222618-8273-4481-b902-ec24e881d8b9
Ayton, Paul M.
960f4b33-3dd1-4930-b902-5ecca3bc7476
Carapeti, Melina
c4685545-f43e-4ca7-9d8c-a790ef5f19fb
Kutok, Jeffery L.
50ee3dc0-d546-40d0-b133-76e5dea66dbe
Snyder, Cynthia S.
01192f77-1b81-4dd0-9995-4f980ea60f4a
Williams, Ifor R.
1740a596-2ec2-4669-9171-71da0b3b7f8e
Cross, Nicholas C.P.
f87650da-b908-4a34-b31b-d62c5f186fe4
Glass, Christopher K.
07c62fbf-c032-493d-95e4-50658313ed31
Cleary, Michael L.
eddf3827-008f-451c-8de9-fb398d919d1a
Gilliland, D. Gary
eb6d954f-0e6e-411b-ac75-7c7dab6de745

Deguchi, Kenji, Ayton, Paul M., Carapeti, Melina, Kutok, Jeffery L., Snyder, Cynthia S., Williams, Ifor R., Cross, Nicholas C.P., Glass, Christopher K., Cleary, Michael L. and Gilliland, D. Gary (2003) MOZ-TIF2-induced acute myeloid leukemia requires the MOZ nucleosome binding motif and TIF2-mediated recruitment of CBP. Cancer Cell, 3 (3), 259-271. (doi:10.1016/S1535-6108(03)00051-5).

Record type: Article

Abstract

The MOZ-TIF2 fusion is associated with acute myeloid leukemia (AML) with inv(8)(p11q13). MOZ is a MYST family histone acetyltransferase (HAT), whereas TIF2 is a nuclear receptor coactivator that associates with CREB binding protein (CBP). Here we demonstrate that MOZ-TIF2 has transforming properties in vitro and causes AML in a murine bone marrow transplant assay. The C2HC nucleosome recognition motif of MOZ is essential for transformation, whereas MOZ HAT activity is dispensable. However, MOZ-TIF2 interaction with CBP through the TIF2 CBP interaction domain (CID) is essential for transformation. These results indicate that nucleosomal targeting by MOZ and recruitment of CBP by TIF2 are critical requirements for MOZ-TIF2 transformation and indicate that MOZ gain of function contributes to leukemogenesis.

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Published date: 2003

Identifiers

Local EPrints ID: 24681
URI: https://eprints.soton.ac.uk/id/eprint/24681
ISSN: 1535-6108
PURE UUID: 355a2a87-6932-4594-bb59-92948c09c4d4
ORCID for Nicholas C.P. Cross: ORCID iD orcid.org/0000-0001-5481-2555

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Date deposited: 04 Apr 2006
Last modified: 06 Jun 2018 12:49

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Contributors

Author: Kenji Deguchi
Author: Paul M. Ayton
Author: Melina Carapeti
Author: Jeffery L. Kutok
Author: Cynthia S. Snyder
Author: Ifor R. Williams
Author: Christopher K. Glass
Author: Michael L. Cleary
Author: D. Gary Gilliland

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