A New Functional Domain of NF1 Molecule at the N-terminal Half (1-1163)

This summer Yoel Kloog's group at Tel Aviv University in Israel found that NF1 gene
product of 2818 amino acids contains an additional functional domain (the first 1163
amino acids) that blocks the oncogenic RAC-PAK-LIMK signaling pathway.

Since the C-terminal RAS GAP domain of NF1 gene product attenuates
normal RAS, and blocks the same potentially oncogenic signaling pathway,
a loss-of-function mutation in either N-terminal (apparently RAC GAP) or
C-terminal (RAS GAP) half causes the abnormal activation of this PAK-LIMK
cascade, eventually transforming normal cells. It still remains to be clarified
why this NF1 molecule contains two separate but functionally similar (redundant)
domains.

It is of great interest to note that CAPE (caffeic acid phenethyl ester)
, the major anti-cancer ingredient in the NZ Propolis extract "Bio 30",
inexpensively available on the market, appears to do the exactly same job
as this N-terminal half of NF1 molecule.


Mol Cell Neurosci. 2009 Aug 7.

The Pre-GAP-related Domain of Neurofibromin Regulates Cell Migration through
the LIM Kinase/Cofilin Pathway.

Starinsky-Elbaz S, Faigenbloom L, Friedman E, Stein R, Kloog, Yoel*
* kloog@post.tau.ac.il

Department of Neurobiology, George S. Wise Faculty of Life Sciences, Tel
Aviv University, 69978 Tel Aviv, Israel.