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J. Biol. Chem., Vol. 277, Issue 40, 36909-36912, October 4, 2002
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,
From The Wistar Institute, Philadelphia, Pennsylvania 19104
Mutations in either of the two tumor suppressor
genes NF1 (neurofibromin) and NF2 (merlin) result in Neurofibromatosis,
a condition predisposing individuals to developing a variety of benign
and malignant tumors of the central and peripheral nervous systems.
Here we report the identification of two distinct NF1-containing complexes, one in the soluble and the other in the particulate fraction
of HeLa extract. We show that the soluble NF1 complex delineates a
large holo-NF1 complex (2 MDa) encompassing the components of a smaller
particulate core-NF1 complex (400 kDa). Purification of the core-NF1
complex followed by mass spectrometric analysis revealed the motor
protein, kinesin-1 heavy chain (HsuKHC/KIF5B), as a catalytic subunit
of both NF-1-containing complexes. Importantly, although NF1 and NF2
are not in a stable association, NF2 is also a component of a distinct
kinesin-1-containing complex. These results point to kinesin-1 as a
common denominator between NF1 and NF2.
Supported by a postdoctoral fellowship from Association pour la
Recherche sur le Cancer (France).
§
Supported by National Institutes of Health Grants CA 90758-01 and
ACS RSG-01-028-01-CNE. To whom correspondence should be addressed: The
Wistar Inst., 3601 Spruce St., Philadelphia, PA 19104. Tel.:
215-898-3896; Fax: 215-898-3986; E-mail:
shiekhattar@wistar.upenn.edu.
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