The t(8;21) chromosomal translocation in acute myelogenous leukemia modifies intranuclear targeting of the AML1/CBFalpha2 transcription factor
Authors
McNeil, Sandra MarieZeng, Congmei
Harrington, Kimberly Stacy
Hiebert, Scott W.
Lian, Jane B.
Stein, Janet L.
Van Wijnen, Andre J.
Stein, Gary S.
Student Authors
Kimberly Stacy HarringtonUMass Chan Affiliations
Department of Cell BiologyDocument Type
Journal ArticlePublication Date
1999-12-21Keywords
Biological Transport; Cell Compartmentation; Cell Nucleus; Core Binding Factor Alpha 2 Subunit; *DNA-Binding Proteins; Humans; Leukemia, Myeloid, Acute; Nuclear Localization Signals; Nuclear Matrix; Oncogene Proteins, Fusion; *Proto-Oncogene Proteins; Transcription Factors; Translocation, GeneticCancer Biology
Metadata
Show full item recordAbstract
Targeting of gene regulatory factors to specific intranuclear sites may be critical for the accurate control of gene expression. The acute myelogenous leukemia 8;21 (AML1/ETO) fusion protein is encoded by a rearranged gene created by the ETO chromosomal translocation. This protein lacks the nuclear matrix-targeting signal that directs the AML1 protein to appropriate gene regulatory sites within the nucleus. Here we report that substitution of the chromosome 8-derived ETO protein for the multifunctional C terminus of AML1 precludes targeting of the factor to AML1 subnuclear domains. Instead, the AML1/ETO fusion protein is redirected by the ETO component to alternate nuclear matrix-associated foci. Our results link the ETO chromosomal translocation in AML with modifications in the intranuclear trafficking of the key hematopoietic regulatory factor, AML1. We conclude that misrouting of gene regulatory factors as a consequence of chromosomal translocations is an important characteristic of acute leukemias.Source
Proc Natl Acad Sci U S A. 1999 Dec 21;96(26):14882-7. Link to article on publisher's site
DOI
10.1073/pnas.96.26.14882Permanent Link to this Item
http://hdl.handle.net/20.500.14038/34184PubMed ID
10611307Related Resources
Link to article in PubMedRights
Publisher PDF posted as allowed by the publisher's author rights policy at http://www.pnas.org/site/aboutpnas/authorfaq.xhtml.ae974a485f413a2113503eed53cd6c53
10.1073/pnas.96.26.14882