The GAP-related domain of neurofibromin attenuates proliferation and downregulates N- and K-Ras activation in Nf1-negative AML cells.

Kelly J. Morgan, Matthew A. Rowley, Stephen M Wiesner, Diane E. Hasz, Brian G Van Ness, David A Largaespada

Research output: Contribution to journalArticle

Abstract

Inactivation of the NF1 tumor suppressor causes myeloproliferative diseases. NF1 encodes a GTPase activating protein (GAP) for Ras. Myeloid cells with loss of NF1 have high levels of Ras-GTP, functionally equivalent to the effects of RAS oncogenes. We investigated the effects of the NF1 GAP-related domain (GRD) in proliferation, apoptosis and Ras-GTP levels in Nf1-negative acute myeloid leukemia (AML) cells. In AML cells, with cooperating mutations, the expression of the neurofibromin GRD causes significant reductions of N- and K-Ras-GTP levels, which is not incompatible with AML cell survival, but which is strongly selected against due to suppression of proliferation.

Original languageEnglish (US)
Pages (from-to)1107-1113
Number of pages7
JournalLeukemia research
Volume31
Issue number8
DOIs
StatePublished - Jan 1 2007

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Neurofibromin 1
GTPase-Activating Proteins
Myeloid Cells
Acute Myeloid Leukemia
Down-Regulation
Guanosine Triphosphate
ras GTPase-Activating Proteins
Oncogenes
Cell Survival
Apoptosis
Mutation
Protein Domains
Neoplasms

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The GAP-related domain of neurofibromin attenuates proliferation and downregulates N- and K-Ras activation in Nf1-negative AML cells. / Morgan, Kelly J.; Rowley, Matthew A.; Wiesner, Stephen M; Hasz, Diane E.; Van Ness, Brian G; Largaespada, David A.

In: Leukemia research, Vol. 31, No. 8, 01.01.2007, p. 1107-1113.

Research output: Contribution to journalArticle

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abstract = "Inactivation of the NF1 tumor suppressor causes myeloproliferative diseases. NF1 encodes a GTPase activating protein (GAP) for Ras. Myeloid cells with loss of NF1 have high levels of Ras-GTP, functionally equivalent to the effects of RAS oncogenes. We investigated the effects of the NF1 GAP-related domain (GRD) in proliferation, apoptosis and Ras-GTP levels in Nf1-negative acute myeloid leukemia (AML) cells. In AML cells, with cooperating mutations, the expression of the neurofibromin GRD causes significant reductions of N- and K-Ras-GTP levels, which is not incompatible with AML cell survival, but which is strongly selected against due to suppression of proliferation.",
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