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8.A.162.  The Cereblon (CRBN) Family

It maintains presynaptic glutamate release and consequently cognitive functions, such as memory and learning, by negatively regulating large-conductance calcium-activated potassium (BK) channels in excitatory neurons (Higgins et al. 2008, Choi et al. 2018). It probably functions by regulating the assembly and neuronal surface expression of BK channels via its interaction with KCNT1 (Higgins et al. 2008). It may also be involved in regulating anxiety-like behaviors via a BK channel-independent mechanism. The IMiD target, CRBN, determines HSP90 activity toward the proper insertion of transmembrane proteins essential in multiple myeloma (Heider et al. 2021). IMiDs, which disrupt the interaction of CRBN with HSP90, folds the amino acid transporter LAT1/CD98hc as a determinant of IMiD activity.


References associated with 8.A.162 family:

Choi, T.Y., S.H. Lee, Y.J. Kim, J.R. Bae, K.M. Lee, Y. Jo, S.J. Kim, A.R. Lee, S. Choi, L.M. Choi, S. Bang, M.R. Song, J. Chung, K.J. Lee, S.H. Kim, C.S. Park, and S.Y. Choi. (2018). Cereblon Maintains Synaptic and Cognitive Function by Regulating BK Channel. J. Neurosci. 38: 3571-3583. 29530986
Heider, M., R. Eichner, J. Stroh, V. Morath, A. Kuisl, J. Zecha, J. Lawatscheck, K. Baek, A.K. Garz, M. Rudelius, F.C. Deuschle, U. Keller, S. Lemeer, M. Verbeek, K.S. Götze, A. Skerra, W.A. Weber, J. Buchner, B.A. Schulman, B. Kuster, V. Fernández-Sáiz, and F. Bassermann. (2021). The IMiD target CRBN determines HSP90 activity toward transmembrane proteins essential in multiple myeloma. Mol. Cell 81: 1170-1186.e10. 33571422
Higgins, J.J., J. Hao, B.E. Kosofsky, and A.M. Rajadhyaksha. (2008). Dysregulation of large-conductance Ca2+-activated K+ channel expression in nonsyndromal mental retardation due to a cereblon p.R419X mutation. Neurogenetics 9: 219-223. 18414909