title: Transport of c-MYC by Kinesin-1 for proteasomal degradation in the cytoplasm.
abstract: c-MYC is an oncogenic transcription factor that is degraded by the proteasome pathway. However, the mechanism that regulates delivery of c-MYC to the proteasome for degradation is not well characterized. Here, the results show that the motor protein complex Kinesin-1 transports c-MYC to the cytoplasm for proteasomal degradation. Inhibition of Kinesin-1 function enhanced ubiquitination of c-MYC and induced aggregation of c-MYC in the cytoplasm. Transport studies showed that the c-MYC aggregates moved from the nucleus to the cytoplasm and KIF5B is responsible for the transport in the cytoplasm. Furthermore, inhibition of the proteasomal degradation process also resulted in an accumulation of c-MYC aggregates in the cytoplasm. Moreover, Kinesin-1 was shown to interact with c-MYC and the proteasome subunit S6a. Inhibition of Kinesin-1 function also reduced c-MYC-dependent transformation activities. Taken together, the results strongly suggest that Kinesin-1 transports c-MYC for proteasomal degradation in the cytoplasm and the proper degradation of c-MYC mediated by Kinesin-1 transport is important for transformation activities of c-MYC. In addition, the results indicate that Kinesin-1 transport mechanism is important for degradation of a number of other proteins as well.
authors.affiliation: Icahn School of Medicine at Mount Sinai, Department of Oncological Sciences, One Gustave L. Levy Place, Box 1130, New York, NY 10029, USA. Electronic address: clement.lee@mssm.edu.
authors.forename: Clement M
authors.initials: CM
authors.lastname: Lee
mesh_terms: D002461:Cell Line, Transformed; D003593:Cytoplasm / Q000187:drug effects / Q000378:metabolism*; D005799:Genes, Dominant; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D016547:Kinesins / Q000378:metabolism*; D007783:Lactones / Q000494:pharmacology; D007976:Leupeptins / Q000494:pharmacology; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D050505:Mutant Proteins / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D020836:Protein Structure, Quaternary; D021381:Protein Transport / Q000187:drug effects; D059748:Proteolysis / Q000187:drug effects; D016271:Proto-Oncogene Proteins c-myc / Q000737:chemistry / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D012395:Rose Bengal / Q000494:pharmacology; D054875:Ubiquitination / Q000187:drug effects
chemical_list: C488101:KIF5B protein, human; D007783:Lactones; D007976:Leupeptins; D008869:Microtubule-Associated Proteins; D050505:Mutant Proteins; D016271:Proto-Oncogene Proteins c-myc; D034741:RNA, Small Interfering; D012395:Rose Bengal; D046988:Proteasome Endopeptidase Complex; D016547:Kinesins; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde
keywords: Kinesin-1; Proteasomal degradation; Trafficking; c-MYC