RAS signaling downstream of NF1 loss-of-function variants

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R-HSA-6802953
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Pathway
Species
Homo sapiens
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RAS signaling downstream of NF1 loss-of-function variants
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NF1 is a RAS GAP that stimulates the intrinsic RAS GTPase activity, thereby shifting the RAS pathway towards the inactive state (reviewed in King et al, 2013). Loss-of-function mutations in NF1 have been identified both in germline diseases like neurofibromatosis 1 and in a range of sporadically occurring cancers. These mutations, which range from complete gene deletions to missense or frameshift mutations, generally decrease NF1 protein levels and abrogate RAS GAP activity in the cells, resulting in constitutive RAS pathway activation (reviewed in Maertens and Cichowski, 2014; Tidyman and Rauen, 2009; Ratner and Miller, 2015).

Literature References
PubMed ID Title Journal Year
23443682 Nonredundant functions for Ras GTPase-activating proteins in tissue homeostasis

King, PD, Lubeck, BA, Lapinski, PE

Sci Signal 2013
19467855 The RASopathies: developmental syndromes of Ras/MAPK pathway dysregulation

Tidyman, WE, Rauen, KA

Curr. Opin. Genet. Dev. 2009
24814062 An expanding role for RAS GTPase activating proteins (RAS GAPs) in cancer

Maertens, O, Cichowski, K

Adv Biol Regul 2014
25877329 A RASopathy gene commonly mutated in cancer: the neurofibromatosis type 1 tumour suppressor

Ratner, N, Miller, SJ

Nat. Rev. Cancer 2015
Participants
Events
Participant Of
hasEvent
Disease
Name Identifier Synonyms
cancer 162 malignant tumor, malignant neoplasm, primary cancer
neurofibromatosis 8712 Neurofibromatosis 1, neurofibromatosis type IV, Acoustic neurofibromatosis, Recklinghausen's neurofibromatosis, neurofibromatosis type 4, central Neurofibromatosis, type IV neurofibromatosis of riccardi, neurofibromatosis type 1, neurofibromatosis type 2, peripheral Neurofibromatosis, von Reklinghausen disease
Authored
Rothfels, K  (2015-08-10)
Reviewed
Stephens, RM  (2016-08-05)
Created
Rothfels, K  (2015-10-02)