TY - JOUR
T1 - Neurofibromin and suppression of tumorigenesis
T2 - beyond the GAP
AU - Mo, Juan
AU - Moye, Stefanie L.
AU - McKay, Renee M.
AU - Le, Lu Q.
N1 - Funding Information:
JM is the recipient of the Early Investigator Research Award from the US Department of Defense (W81XWH1910687). LQL held a Career Award for Medical Scientists from the Burroughs Wellcome Fund and is the Thomas L. Shield, M.D. endowed Professor in Dermatology. He is supported by funding from the US Department of Defense, the National Cancer Institute of the NIH (R01 CA166593) and the Developmental and Hyperactive RAS Tumor SPORE (U54 CA196519); the Neurofibromatosis Therapeutic Acceleration Program; the NF1 Research Consortium Fund; and the Giorgio Foundation.
Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2022/2/25
Y1 - 2022/2/25
N2 - Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disease and one of the most common inherited tumor predisposition syndromes, affecting 1 in 3000 individuals worldwide. The NF1 gene encodes neurofibromin, a large protein with RAS GTP-ase activating (RAS-GAP) activity, and loss of NF1 results in increased RAS signaling. Neurofibromin contains many other domains, and there is considerable evidence that these domains play a role in some manifestations of NF1. Investigating the role of these domains as well as the various signaling pathways that neurofibromin regulates and interacts with will provide a better understanding of how neurofibromin acts to suppress tumor development and potentially open new therapeutic avenues. In this review, we discuss what is known about the structure of neurofibromin, its interactions with other proteins and signaling pathways, its role in development and differentiation, and its function as a tumor suppressor. Finally, we discuss the latest research on potential therapeutics for neurofibromin-deficient neoplasms.
AB - Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disease and one of the most common inherited tumor predisposition syndromes, affecting 1 in 3000 individuals worldwide. The NF1 gene encodes neurofibromin, a large protein with RAS GTP-ase activating (RAS-GAP) activity, and loss of NF1 results in increased RAS signaling. Neurofibromin contains many other domains, and there is considerable evidence that these domains play a role in some manifestations of NF1. Investigating the role of these domains as well as the various signaling pathways that neurofibromin regulates and interacts with will provide a better understanding of how neurofibromin acts to suppress tumor development and potentially open new therapeutic avenues. In this review, we discuss what is known about the structure of neurofibromin, its interactions with other proteins and signaling pathways, its role in development and differentiation, and its function as a tumor suppressor. Finally, we discuss the latest research on potential therapeutics for neurofibromin-deficient neoplasms.
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U2 - 10.1038/s41388-021-02156-y
DO - 10.1038/s41388-021-02156-y
M3 - Review article
C2 - 35066574
AN - SCOPUS:85123473825
SN - 0950-9232
VL - 41
SP - 1235
EP - 1251
JO - Oncogene
JF - Oncogene
IS - 9
ER -