RGD Reference Report - Regulation of cyclin-dependent kinase 4 translation through CUG-binding protein 1 and microRNA-222 by polyamines. - Rat Genome Database

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Regulation of cyclin-dependent kinase 4 translation through CUG-binding protein 1 and microRNA-222 by polyamines.

Authors: Xiao, Lan  Cui, Yu-Hong  Rao, Jaladanki N  Zou, Tongtong  Liu, Lan  Smith, Alexis  Turner, Douglas J  Gorospe, Myriam  Wang, Jian-Ying 
Citation: Xiao L, etal., Mol Biol Cell. 2011 Sep;22(17):3055-69. doi: 10.1091/mbc.E11-01-0069. Epub 2011 Jul 7.
RGD ID: 151893503
Pubmed: PMID:21737690   (View Abstract at PubMed)
PMCID: PMC3164454   (View Article at PubMed Central)
DOI: DOI:10.1091/mbc.E11-01-0069   (Journal Full-text)

The amino acid-derived polyamines are organic cations that are essential for growth in all mammalian cells, but their exact roles at the molecular level remain largely unknown. Here we provide evidence that polyamines promote the translation of cyclin-dependent kinase 4 (CDK4) by the action of CUG-binding protein 1 (CUGBP1) and microRNA-222 (miR-222) in intestinal epithelial cells. Both CUGBP1 and miR-222 were found to bind the CDK4 mRNA coding region and 3'-untranslated region and repressed CDK4 translation synergistically. Depletion of cellular polyamines increased cytoplasmic CUGBP1 abundance and miR-222 levels, induced their associations with the CDK4 mRNA, and inhibited CDK4 translation, whereas increasing the levels of cellular polyamines decreased CDK4 mRNA interaction with CUGBP1 and miR-222, in turn inducing CDK4 expression. Polyamine-deficient cells exhibited an increased colocalization of tagged CDK4 mRNA with processing bodies; this colocalization was abolished by silencing CUGBP1 and miR-222. Together, our findings indicate that polyamine-regulated CUGBP1 and miR-222 modulate CDK4 translation at least in part by altering the recruitment of CDK4 mRNA to processing bodies.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

Objects Annotated

Genes (Rattus norvegicus)
Cdk4  (cyclin-dependent kinase 4)
Celf1  (CUGBP, Elav-like family member 1)
Mir222  (microRNA 222)


Additional Information