NPM1 in AML

Pathway ID: SIGNOR-AML-NP1

Description: Nucleophosmin (NPM1) is the most frequently mutated gene in Acute Myeloid Leukemia (AML). The protein shows a wide tissue distribution, shuttls between nucleus and cytoplasm, but is mainly localized at nucleoli. NPM1 contains a N-terminal nuclear export signal (NES), a bipartite nuclear localization signal (NLS) and a C-terminal nucleolar localization signal (NoLS). NPM1 mutations in AML are always heterozygous and mutually exclusive with AML carrying recurrent genetic abnormalities. In all instances, the nucleolar localization signal is compromised and a new NES appears. In AML with mutated NPM1, the variant nucleophosmin protein is stably delocalized in the cytoplasm and therefore referred to as NPM1c+ (for cytoplasmic positive). The NPM1c+ protein can bind the wild-type counterpart (through the N-terminal portion) and dominantly delocalize the majority of NPM1 in the cytoplasm. NPM1c+ delocalize in the cytoplasm also its physical interactors, the tumor suppressors p14Arf and Fwb7gamma, causing their degradation, which cause decreased levels of p53 and increased c-Myc half life. Moreover NPM1c+ leads to polyubiquitination and degradation of the tumor suppressor PTEN. PMID: 23436734, 18625840

Curated by: miannu

9 Seed Entities

Organism:
Name Primary ID
Apoptosis SIGNOR-PH2
CDKN2A Q8N726
Proliferation SIGNOR-PH4
FBXW7 Q969H0
NPM1 P06748
CDKN2A P42771
TP53 P04637
MDM2 Q00987
MYC P01106