Delineating domains and functions of NUP98 contributing to the leukemogenic activity of NUP98-HOX fusions Journal Articles

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abstract

To determine the contribution of the common N-terminal truncation of NUP98 in NUP98-translocations resulting in acute myeloid leukemia, we have conducted a structure-function analysis of NUP98 in the context of NUP98-HOXA10HD, a novel, canonical NUP98-Hox fusion that significantly enhances the self-renewal capacity of hematopoietic stem cells and collaborates with Meis1 to induce AML in our mouse models. Our results identify that NUP98 functions by transcriptional activation likely by recruitment of CBP/p300 via its FG/GLFG repeats. In contrast, the functional interaction of NUP98 with Rae1 or the anaphase promoting complex appears non-essential for its role in NUP98-leukemogenic fusions.

authors

Yung, Eric
Sekulovic, Sanja
Argiropoulos, Bob
Lai, Courteney K
Leung, Malina
Berg, Tobias
Vollett, Sarah
Chang, Vicky Chi-Dan
Wan, Adrian
Wong, Sandy
Humphries, R Keith

status

published

publication date

April 2011

has subject area

1103 Clinical Sciences (FoR)
Acute Disease (MeSH)
Amino Acid Sequence (MeSH)
Animals (MeSH)
Binding Sites (MeSH)
Bone Marrow Cells (MeSH)
Cell Transformation, Neoplastic (MeSH)
Cells, Cultured (MeSH)
Female (MeSH)
Homeobox A10 Proteins (MeSH)
Homeodomain Proteins (MeSH)
Immunology (Science Metrix)
Kaplan-Meier Estimate (MeSH)
Leukemia, Myeloid (MeSH)
Luminescent Proteins (MeSH)
Male (MeSH)
Mice (MeSH)
Mice, Inbred C57BL (MeSH)
Mutation (MeSH)
Myeloid Ecotropic Viral Integration Site 1 Protein (MeSH)
Neoplasm Proteins (MeSH)
Nuclear Matrix-Associated Proteins (MeSH)
Nuclear Pore Complex Proteins (MeSH)
Nucleocytoplasmic Transport Proteins (MeSH)
Oncogene Proteins, Fusion (MeSH)
Protein Binding (MeSH)
Repetitive Sequences, Amino Acid (MeSH)
p300-CBP Transcription Factors (MeSH)

published in

Leukemia Research Journal