NPM1-ALK-dependent JUNB gene transcription

Stable Identifier
R-HSA-9725342
Type
Reaction [omitted]
Species
Homo sapiens
Compartment
cytosol, nucleoplasm
ReviewStatus
5/5
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NPM1-ALK-dependent JUNB gene transcription
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NPM-ALK is known to drive expression of AP1 transcription factor family members, and AP1 targets are differentially expressed in ALK+ ALCLs compared to ALK- (Staber et al, 2007; Turner et al, 2007; Levantaki et al, 2007; Schleussner et al, 2018; reviewed in Ducray et al, 2019; Hallberg and Palmer, 2013; Garces de los Fayos Alonso et al, 2018). JUNB gene expression is driven downstream of NPM-ALK activity in anaplastic large cell lymphoma in a manner that is dependent on NPM-ALK kinase activity. NPM-ALK-mediated signaling stimulates transcriptional upregulation of JUNB through the MAP kinase signaling cascade and promotes accumulation of the JUNB protein through the PI3K/AKT signaling pathway. Consistent with this, treatment of NPM-ALK-expressing cells with either a MEK or a p70S6K inhibitor decreases JUNB levels and impairs cellular proliferation (Piva et al, 2006; Staber et al, 2007). Expression of AP1 components such as JUNB, JUN and FRA2 contribute to apoptosis and proliferation in ALCL cells (Mathas et al, 2002; Staber et al, 2007; Pearson et al, 2011).
Literature References
PubMed ID Title Journal Year
12145210 Aberrantly expressed c-Jun and JunB are a hallmark of Hodgkin lymphoma cells, stimulate proliferation and synergize with NF-kappa B

Krappmann, D, Anagnostopoulos, I, Jundt, F, Lietz, A, Dörken, B, Mathas, S, Mechta-Grigoriou, F, Hinz, M, Scheidereit, C, Stein, H, Bommert, K

EMBO J 2002
29597249 The Role of Activator Protein-1 (AP-1) Family Members in CD30-Positive Lymphomas

Garces de Los Fayos Alonso, I, Lagger, S, Turner, SD, Liang, HC, Kenner, L, Merkel, O

Cancers (Basel) 2018
17111047 Functional validation of the anaplastic lymphoma kinase signature identifies CEBPB and BCL2A1 as critical target genes

Chiarle, R, Piva, R, Inghirami, G, Ruggeri, BA, Boccalatte, F, Cheng, M, Palestro, G, Costa, G, Lombardi, L, Pellegrino, E, Neri, A, Agnelli, L, Mattioli, M

J Clin Invest 2006
31366041 The Transcriptional Roles of ALK Fusion Proteins in Tumorigenesis

Ducray, SP, Turner, SD, Garland, GD, Natarajan, K, Egger, G

Cancers (Basel) 2019
17110082 The NPM-ALK tyrosine kinase mimics TCR signalling pathways, inducing NFAT and AP-1 by RAS-dependent mechanisms

Yeung, D, Turner, SD, Hadfield, K, Alexander, DR, Cook, SJ

Cell Signal 2007
17690253 The oncoprotein NPM-ALK of anaplastic large-cell lymphoma induces JUNB transcription via ERK1/2 and JunB translation via mTOR signaling

Ott, RG, Hrzenjak, A, Linkesch, W, Bambach, I, Bergler, H, Haq, N, Fuchs, C, Funato, K, Dirks, WG, Vesely, P, Sexl, V, Schauer, S, Staber, PB, Kadin, ME, Kenner, L, Sternberg, DW, Hoefler, G

Blood 2007
21326808 NPM-ALK and the JunB transcription factor regulate the expression of cytotoxic molecules in ALK-positive, anaplastic large cell lymphoma

Ingham, RJ, Bacani, JT, Lai, R, Pearson, JD, Lee, JK

Int J Clin Exp Pathol 2011
17416736 NPM-ALK oncogenic kinase promotes cell-cycle progression through activation of JNK/cJun signaling in anaplastic large-cell lymphoma

Drakos, E, Rassidakis, GZ, Elenitoba-Johnson, KS, Lim, MS, Claret, FX, Medeiros, LJ, Leventaki, V

Blood 2007
29588546 The AP-1-BATF and -BATF3 module is essential for growth, survival and TH17/ILC3 skewing of anaplastic large cell lymphoma

Piva, R, Damm-Welk, C, Scheidereit, C, Anagnostopoulos, I, Romagnani, C, Dörken, B, Lenz, G, Liang, HC, Stoiber, D, Woessmann, W, Niedobitek, A, von Hoff, L, Durek, P, Janz, M, Kaergel, E, Hinze, C, Gillissen, B, Costanza, M, Mathas, S, Turner, SD, Kenner, L, Grau, M, Merkel, O, Hummel, F, Sczakiel, HL, Schleussner, N, Griffin, PR, Hummel, M, Jöhrens, K

Leukemia 2018
24060861 Mechanistic insight into ALK receptor tyrosine kinase in human cancer biology

Palmer, RH, Hallberg, B

Nat. Rev. Cancer 2013
Participants
Input
Output
Participates
as an event of
This event is regulated
Positively by
Regulator
NPM1(1-117)-p-7Y ALK(1058-1620) fusion dimer [nucleoplasm] (Homo sapiens)
Regulator
p-T,Y MAPK monomers and dimers [nucleoplasm] (Homo sapiens)
Disease
Name Identifier Synonyms
cancer DOID:162 malignant tumor, malignant neoplasm, primary cancer
Authored
Rothfels, K  (2021-03-30)
Reviewed
Inghirami, G  (2021-05-04)
Created
Rothfels, K  (2021-03-29)
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