BACKGROUND: There is often a poor correlation observed between protein and RNA 
in eukaryotic systems, supporting the emerging pardigm that many of the 
abnormalities in a cancer cell's proteome may be achieved by differential 
recruitment of mRNAs to polysomes referred to as the translational profile. The 
MCT-1 oncogene product has recently been shown to interact with the cap complex 
and to modulate the translational profile of cell lines when MCT-1 was highly 
expressed. The MCT-1 protein modifies mRNA translational profiles through its 
interaction with DENR/DRP, a protein containing an SUI1 domain involved in 
recognition of the translation initiation codon. It has been shown previously 
that the protein levels of DENR/DRP go up in parallel with increasing cell 
density, however the mechanism(s) underlying this increase is poorly understood 
at present. The 3'-untranslated region (3'UTR) of DENR/DRP was found to have a 
high number of uracyl (U)- and adenine (A)-rich sequences (AREs). Many 
RNA-binding proteins (RBPs) have been shown to recognize and bind to mRNAs that 
contains AREs generally present in the 3'UTR of mRNAs. RBPs binding to AREs such 
as AUF1, BRF1, KSRP, and TTP are known to regulate mRNA turnover, while TIAR and 
TIA-1 influence mRNA translation.
MATERIALS AND METHODS: We assessed the association of several ARE binding 
proteins with DENR/DRP mRNA by reverse transcription of the RNA obtained after 
immunoprecipitation of cell lysates from HEK 293 cells growing at varying levels 
of cell density. HEK 293 cells were transfected with an AUF1 silencing vector 
(shRNA), and protein levels of DENR/DRP were analyzed by Western blotting.
RESULTS: We demonstrated that both HuR and AUF1 bind to discrete regions of 
DENR/DRP mRNA and that AUF1 silencing increases DENR/DRP protein levels.
CONCLUSION: Our data established a cell density-dependent interaction of AUF1 
protein with DENR/DRP mRNA that modulates DENR/DRP protein levels.