Mip/LIN-9 regulates the expression of B-Myb and the induction of cyclin A, cyclin B, and CDK1

J Biol Chem. 2007 Jan 5;282(1):168-75. doi: 10.1074/jbc.M609924200. Epub 2006 Nov 10.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Base Sequence
  • CDC2 Protein Kinase / metabolism*
  • Cell Cycle Proteins / biosynthesis*
  • Cell Line, Tumor
  • Cyclin A / physiology*
  • Cyclin B / physiology*
  • DNA-Binding Proteins / biosynthesis*
  • Gene Expression Regulation*
  • Humans
  • Mice
  • Molecular Sequence Data
  • NIH 3T3 Cells
  • Nuclear Proteins
  • Trans-Activators / biosynthesis*
  • Tumor Suppressor Proteins / metabolism
  • Tumor Suppressor Proteins / physiology*

Substances

  • Cell Cycle Proteins
  • Cyclin A
  • Cyclin B
  • DNA-Binding Proteins
  • LIN-9 protein, mouse
  • LIN9 protein, human
  • MYBL2 protein, human
  • Mybl2 protein, mouse
  • Nuclear Proteins
  • Trans-Activators
  • Tumor Suppressor Proteins
  • CDC2 Protein Kinase