Filamins but not Janus kinases are substrates of the ASB2α cullin-ring E3 ubiquitin ligase in hematopoietic cells.
The ASB2α protein is the specificity subunit of an E3 ubiquitin ligase complex involved in hematopoietic differentiation and is proposed to exert its effects by regulating the turnover of specific proteins. Three ASB2α substrates have been described so far: the actin-binding protein filamins, the Mixed Lineage Leukemia protein, and the Janus kinases 2 and 3. To determine the degradation of which substrate drives ASB2α biological effects is crucial for the understanding of ASB2α functions in hematopoiesis. Here, we show that neither endogenous nor exogenously expressed ASB2α induces degradation of JAK proteins in hematopoietic cells. Furthermore, we performed molecular modeling to generate the first structural model of an E3 ubiquitin ligase complex of an ASB protein bound to one of its substrates.
CNRS, IPBS (Institut de Pharmacologie et de Biologie Structurale), 205 route de Narbonne BP64182, F-31077 Toulouse, France.
Isabelle
I
Lamsoul
Monique
M
Erard
Peter F M
PF
van der Ven
Pierre G
PG
Lutz
D002460:Cell Line; D003285:Contractile Proteins / Q000378:metabolism*; D044842:Cullin Proteins / Q000378:metabolism*; D064448:Filamins; D006801:Humans; D053612:Janus Kinases / Q000378:metabolism*; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism; D008840:Microfilament Proteins / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D050826:Suppressor of Cytokine Signaling Proteins / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*
C437987:ASB2 protein, human; D003285:Contractile Proteins; D044842:Cullin Proteins; D064448:Filamins; D008840:Microfilament Proteins; D050826:Suppressor of Cytokine Signaling Proteins; D044767:Ubiquitin-Protein Ligases; D053612:Janus Kinases