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In addition to the regulation of key proteins and signal pathways related to cell metabolism, CRBN has effects on cell proliferation and apoptosis.
Recent studies also found that CRBN has a negative regulation role of CD4+ T cell activation.
reported, in 2015, that CRBN was recruited to aggresome and had a protective effect against extracellular stresses, such as ubiquitin-proteasome system (UPS) impairment and oxidative stress.
CRBN Is the Target Protein of IMiDs and Is Responsible for Their Multiple Functions
Accumulating evidence indicated that CRBN was responsible for the teratogenic activities of thalidomide, until 2010, when a group of scientists proved that CRBN was the bona fide target of thalidomide .
fgf8 can be upregulated by the CD147-MCT1 complex whose activity is promoted by CRBN through their combination.
In addition to the Ikaros family members, many other interesting proteins participating in important physiological processes also bind to CRBN and are regulated by IMiDs in a ubiquitin-dependent mechanism [37, 43].
In addition to the ubiquitin-dependent pathway mentioned above, a recent study reported a ubiquitin-independent pathway through which CRBN mediates the antimyeloma effect of IMiDs.
identified that argonaute 2 (AGO2), as a CRBN binding partner, plays an important role in regulating angiogenesis and MM cell survival.
CRBN and Its Downstream Protein Expression Level Affect the Response Rate of IMiDs.
In line with the analysis of clinical data, the sensitivity to IMiDs is strongly related to CRBN protein level on a cellular level.
The same group compared the CRBN expression level of IMiDs primary resistance MM cell lines such as OCI-My5 and OPM1 with relatively sensitive cell lines such as MM1S and OPM2.
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