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THE JOURNAL OF BIOLOGICAL CHEMISTRY VOL. 289, NO. 34, pp. 23343?3352, August 22, 2014 ?2014 by The American Society for Biochemistry and Molecular Biology, Inc. Published in the U.S.A.Functional Effects of a Pathogenic Mutation in Cereblon (CRBN) on the Regulation of Protein Synthesis through the AMPK-mTOR CascadeReceived for publication, October 1, 2013, and in revised form, June 29, 2014 Published, JBC Papers in Press, July three, 2014, DOI 10.1074/jbc.M113.Kwang Min Lee1, Seung-Joo Yang, Ja-Hyun Choi, and Chul-Seung Park2 In the School of Life Sciences, Cell Dynamics Analysis Center and National Leading Research Laboratory, Gwangju Institute Science and Technology (GIST), Gwangju, 500-712, The Republic of KoreaBackground: Deficiency or nonsense mutation of CRBN causes memory deficits. Outcomes: Truncated CRBN has insufficient affinity for AMPK and cannot modulate the AMPK-mTOR pathway. Conclusion: CRBN modulates protein synthesis by means of the AMPK-mTOR pathway, and might be vital for particular types of memory encoding. Significance: Our findings recommend the first mGluR3 Species plausible mechanism for the phenotype resulting from the CRBN mutation. Initially identified as a protein implicated in human mental deficit, cereblon (CRBN) was lately recognized as a damaging regulator of adenosine monophosphate-activated protein kinase (AMPK) in vivo and in vitro. Right here, we present results showing that CRBN can properly regulate new protein synthesis by means of the mammalian target of rapamycin (mTOR) signaling pathway, a downstream target of AMPK. Whereas deficiency of Crbn repressed protein translation by way of activation in the AMPKmTOR cascade in Crbn-knock-out mice, ectopic expression with the wild-type CRBN enhanced protein.