Mip/LIN-9 regulates the expression of B-Myb and the induction of cyclin A, cyclin B, and CDK1.
Members of the novel family of proteins that include Drosophila Mip130, Caenorhabditis elegans LIN-9, and mammalian LIN-9 intervene in different cellular functions such as regulation of transcription, differentiation, transformation, and cell cycle progression. Here we demonstrate that LIN-9, designated as Mip/LIN-9, interacts with B-Myb but not with c-Myb or A-Myb. Mip/LIN-9 regulates the expression of B-Myb in a post-transcriptional manner, and its depletion not only decreases the level of the B-Myb protein but also affects the expression of S phase and mitotic genes (i.e. cyclin A, CDK1, and cyclin B). The critical role of Mip/LIN-9 on the expression of S and G(2)/M genes is further supported by the finding that coexpression of Mip/LIN-9 and B-Myb results in the activation of cyclin A and cyclin B promoter-luciferase reporters, and both proteins are detected on the cyclin A and B promoters. Interestingly, although Mip/LIN-9 promoter occupancy peaks earlier than B-Myb, the highest levels of expression of cyclins A and B correlate with the maximum binding of B-Myb to these promoters. These data support the concept that Mip/LIN-9 is required for the expression of B-Myb, and both proteins collaborate in the control of the cell cycle progression via the regulation of S phase and mitotic cyclins.
Pilkinton
Mark
M
Department of Pharmacology, University of Illinois, Chicago, Illinois 60612, USA.
Sandoval
Raudel
R
Song
Julie
J
Ness
Scott A
SA
Colamonici
Oscar R
OR
D000818:Animals; D001483:Base Sequence; D016203:CDC2 Protein Kinase / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000096:biosynthesis*; D045744:Cell Line, Tumor; D019925:Cyclin A / Q000502:physiology*; D019926:Cyclin B / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D041681:NIH 3T3 Cells; D009687:Nuclear Proteins; D015534:Trans-Activators / Q000096:biosynthesis*; D025521:Tumor Suppressor Proteins / Q000378:metabolism / Q000502:physiology*
D018797:Cell Cycle Proteins; D019925:Cyclin A; D019926:Cyclin B; D004268:DNA-Binding Proteins; C512498:LIN-9 protein, mouse; C501563:LIN9 protein, human; C064352:MYBL2 protein, human; C499306:Mybl2 protein, mouse; D009687:Nuclear Proteins; D015534:Trans-Activators; D025521:Tumor Suppressor Proteins; D016203:CDC2 Protein Kinase