NPM1-ALK binds NPM1 and FOXM1

Stable Identifier
R-HSA-9851090
Type
Reaction [binding]
Species
Homo sapiens
Compartment
nucleoplasm
ReviewStatus
5/5
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NPM1-ALK binds NPM1 and FOXM1
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Nuclear NPM-ALK binds to endogenous full-length NPM and FOXM1 in ALK+ ALCL cells as assessed by co-immunoprecipitation (Haque et al, 2019). Endogenous NPM1 likely bridges the interaction between NPM-ALK and FOXM1, as the FOXM1-binding region of NPM1 is not conserved in the fusion protein and NPM1-ALK has been shown to form heterodimers with NPM1 (Box et al, 2016; Khan et al, 2015; Bhat et al, 2011). Formation of this complex is required for FOXM1-dependent expression of target genes such as CCNB1 (Cyclin B1), and consistent with this, both NPM-ALK and FOXM1 are detected in complex with a biotinylated FOXM1-consensus containing DNA target in ALCL lines and bind to the CCNB1 promoter as assessed by ChIP (Haque et al, 2019).
STAT3 likely contributes to the NPM1-ALK:FOXM1 signaling axis, as lentiviral knockdown of FOXM1 decreases phosphorylation of both STAT3 and NPM1-ALK, as well as decreasing expression of CCNB1. The significance of FOXM1-dependent phosphorylation of STAT3 and NPM1-ALK remains to be clarified (Haque et al, 2019).
Literature References
PubMed ID Title Journal Year
21979956 Nucleophosmin interacts with FOXM1 and modulates the level and localization of FOXM1 in human cancer cells

Jagadeeswaran, R, Bhat, UG, Gartel, AL, Halasi, M

J Biol Chem 2011
31390744 NPM-ALK Is a Key Regulator of the Oncoprotein FOXM1 in ALK-Positive Anaplastic Large Cell Lymphoma

Wang, P, Haque, M, Turner, SD, Barger, CJ, Huang, YH, Chen, W, Almowaled, M, Karpf, AR, Lai, R, Li, J

Cancers (Basel) 2019
27553022 Nucleophosmin: from structure and function to disease development

Paquet, N, O'Byrne, KJ, Bolderson, E, Boucher, D, Adams, MN, Box, JK, Richard, DJ

BMC Mol Biol 2016
Participants
Input
Output
Participates
as an event of
Disease
Name Identifier Synonyms
anaplastic large cell lymphoma DOID:0050744
cancer DOID:162 malignant tumor, malignant neoplasm, primary cancer
Authored
Rothfels, K  (2023-10-14)
Reviewed
Turner, S  (2023-11-08)
Created
Rothfels, K  (2023-10-12)
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