CBL mutants don't ubiquitinate FLT3

Stable Identifier
R-HSA-9706356
Type
Reaction [transition]
Species
Homo sapiens
Compartment
plasma membrane
ReviewStatus
5/5
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CBL mutants don't ubiquitinate FLT3
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CBL missense and internal deletion mutants have been identified in acute and chronic myeloid leukemias, as well as in myelodysplastic syndromes and other cancers. These mutations abrogate the ubiquitin ligase activity of the enzyme thus impairing the downregulation of FLT3 and resulting in enhanced signaling and transformation (Sargin et al, 2007; Reindl et al, 2009; Caligiuri et al, 2007; Abbas et al, 2008).
Literature References
PubMed ID Title Journal Year
18698078 Exon 8 splice site mutations in the gene encoding the E3-ligase CBL are associated with core binding factor acute myeloid leukemias

Rotmans, G, Abbas, S, Valk, PJ, Löwenberg, B

Haematologica 2008
19276253 CBL exon 8/9 mutants activate the FLT3 pathway and cluster in core binding factor/11q deletion acute myeloid leukemia/myelodysplastic syndrome subtypes

Buske, C, Duyster, J, Reindl, C, Spiekermann, K, Vempati, S, Bohlander, SK, Humphries, KR, Greif, PA, Mellert, G, Argiropoulos, B, Hiddemann, W, Quentmeier, H, Benthaus, T, Petropoulos, K

Clin Cancer Res 2009
17475912 Novel c-CBL and CBL-b ubiquitin ligase mutations in human acute myeloid leukemia

Caligiuri, MA, Perrotti, D, Wei, M, Arnoczky, KJ, Wen, J, Whitman, SP, Bloomfield, CD, Wang, L, Marburger, TB, Yu, J, Briesewitz, R

Blood 2007
17446348 Flt3-dependent transformation by inactivating c-Cbl mutations in AML

Berdel, WE, Grundler, R, Serve, H, Duyster, J, Brandts, C, Tickenbrock, L, Choudhary, C, Koschmieder, S, Dikic, I, Müller-Tidow, C, Schwäble, J, August, B, Thiessen, C, Crosetto, N, Sargin, B, Rensinghoff, M, Bandi, SR, Schmidt, MHH

Blood 2007
Participants
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Catalyst Activity

ubiquitin protein ligase activity of Active FLT3:CBL mutants [plasma membrane]

Physical Entity
Active FLT3:CBL mutants [plasma membrane] (Homo sapiens)
Activity
ubiquitin protein ligase activity (GO:0061630)
Normal reaction
Ubiquitination of FLT3 (Homo sapiens)
Functional status

Loss of function of Active FLT3:CBL mutants [plasma membrane]

Normal Entity
Disease Entity
Status
Disease
Name Identifier Synonyms
cancer DOID:162 malignant tumor, malignant neoplasm, primary cancer
Authored
Rothfels, K  (2020-11-06)
Reviewed
Kazi, JU  (2020-11-06)
Created
Rothfels, K  (2020-11-04)
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