The homeobox transcription factor MEIS2 is a regulator of cancer cell survival and IMiDs activity in multiple myeloma. modulation by bromodomain and Extra-Terminal (BET) protein inhibitors
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 CRBN facilitating the subsequent activation of a CRL4 CRBN IMiD -E3-ubiquitin ligase activity and proteasome-mediated degradation of critical substrates regulators of Multiple Myeloma (MM) cell survival and proliferation.