The 3' untranslated region of the cyclin B mRNA is not sufficient to enhance the synthesis of cyclin B during a mitotic block in human cells.
Antimitotic agents are frequently used to treat solid tumors and hematologic malignancies. However, one major limitation of antimitotic approaches is mitotic slippage, which is driven by slow degradation of cyclin B during a mitotic block. The extent to which cyclin B levels decline is proposed to be governed by an equilibrium between cyclin B synthesis and degradation. It was recently shown that the 3' untranslated region (UTR) of the murine cyclin B mRNA contributes to the synthesis of cyclin B during mitosis in murine cells. Using a novel live-cell imaging-based technique allowing us to study synthesis and degradation of cyclin B simultaneously at the single cell level, we tested here the role of the human cyclin B 3'UTR in regulating cyclin B synthesis during mitosis in human cells. We observed that the cyclin B 3'UTR was not sufficient to enhance cyclin B synthesis in human U2Os, HeLa or hTERT RPE-1 cells. A better understanding of how the equilibrium of cyclin B is regulated in mitosis may contribute to the development of improved therapeutic approaches to prevent mitotic slippage in cancer cells treated with antimitotic agents.
Department of Hematology, Oncology and Stem Cell Transplantation, University Medical Center, Freiburg, Germany.
Dominik
D
Schnerch
Marie
M
Follo
Julia
J
Felthaus
Monika
M
Engelhardt
Ralph
R
Wäsch
D020413:3' Untranslated Regions / Q000235:genetics*; D000818:Animals; D002460:Cell Line; D002877:Chromosomes, Human / Q000378:metabolism; D019926:Cyclin B / Q000096:biosynthesis* / Q000235:genetics*; D017930:Genes, Reporter; D006801:Humans; D007700:Kinetics; D051379:Mice; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism; D008938:Mitosis / Q000187:drug effects / Q000235:genetics*; D017239:Paclitaxel / Q000494:pharmacology; D059748:Proteolysis / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D020413:3' Untranslated Regions; D019926:Cyclin B; D012333:RNA, Messenger; D017239:Paclitaxel