2019年4月11日 · Emerging evidence suggests that IMiDs can block MEIS2 from binding to CRBN facilitating the subsequent activation of a CRL4CRBNIMiD-E3-ubiquitin ligase activity and proteasome-mediated...

2014年8月7日 · Our studies suggest that IMiDs block endogenous substrates (MEIS2) from binding to CRL4(CRBN) while the ligase complex is recruiting IKZF1 or IKZF3 for degradation. This dual activity implies that small molecules can modulate an E3 ubiquitin ligase and thereby upregulate or downregulate the ubiquitination of proteins.

2024年11月5日 · Further biochemical analyses revealed that CDK4/6 inhibition rapidly accelerated the displacement of MEIS2 from CRBN within one hour of Len treatment, concurrent with enhanced ubiquitination and degradation of IKZF1 and IKZF3 in both MM cell lines and primary BMMCs.

2014年7月16日 · Our studies suggest that IMiDs block endogenous substrates (MEIS2) from binding to CRL4 CRBN while the ligase complex is recruiting IKZF1 or IKZF3 for degradation. This dual activity implies...

2019年4月11日 · The transcription factor Myeloid Ecotropic Insertion Site 2 (MEIS2) has been identified as a cellular substrate of the E3-ubiquitin ligase complex CRL4-cereblon (CRL4 CRBN) in crystal structure and by biochemical screen.

2024年11月5日 · This resulted in a ~3-fold increase in the MEIS2 to CRBN ratio in IMiD refractory patients, implicating a role for MEIS2 in inhibiting CRBN and promoting clinical resistance to IMiD therapy. In addition, high expression of core genes that promote cell cycle progression through early G1 ( CDK4 and CDK6 ) and late G1 ( E2F1, CDK2, CCNA2 ) also ...

2019年4月11日 · The transcription factor Myeloid Ecotropic Insertion Site 2 (MEIS2) has been identified as a cellular substrate of the E3-ubiquitin ligase complex CRL4-cereblon ( CRL4 CRBN) in crystal structure and by biochemical screen. Emerging evidence suggests that IMiDs can block MEIS2 from binding to …

This resulted in a ~3-fold increase in the MEIS2 to CRBN ratio in IMiD refractory patients, implicating a role for MEIS2 in inhibiting CRBN and promoting clinical resistance to IMiD therapy. In addition, high expression of core genes that promote cell cycle progression through early G1 ( CDK4 and CDK6 ) and late G1 ( E2F1, CDK2, CCNA2 ) also ...

2013年12月5日 · Our studies suggest that IMiDs block endogenous substrates (MEIS2) from binding to CRL4 (CRBN) while the ligase complex is recruiting IKZF1 or IKZF3 for degradation. This dual activity implies that small molecules can modulate an E3 ubiquitin ligase and thereby upregulate or downregulate the ubiquitination of proteins.

2016年12月2日 · Recent crystal structure studies in conjunction with biochemical screen have identified MEIS2 as an endogenous substrate of CRBN. IMiDs apparently bind CRBN and block MEIS2 from binding to CRBN, thereby facilitating the recruitment of transcription factors IKZF1 and IKZF3 to CRL4 CRBN for degradation. This then leads to loss of IRF4, a target ...