Identification of the active gene coding for the metastasis-associated 37LRP/p40 multifunctional protein

Area of Science:

• Molecular Biology
• Cancer Research
• Genomics

Background:

• The 37LRP/p40 polypeptide is upregulated in invasive and metastatic cancer cells.
• It functions as the precursor to the 67-kD laminin receptor (67LR) and a ribosomal protein.
• Identifying the active 37LRP/p40 gene is essential for understanding 67LR expression in cancer.

Purpose of the Study:

• To report the gene structure and regulatory sequences of the 37LRP/p40 gene.
• To characterize the active 37LRP/p40 gene, which has been elusive due to pseudogenes.
• To provide a foundation for isolating the human gene and understanding its role in metastasis.

Main Methods:

• Utilized the chicken genome, which possesses a single 37LRP/p40 gene copy.
• Determined gene structure (exons, introns) and identified regulatory elements.
• Employed RNase protection assay and primer extension to analyze transcription initiation sites.
• Conducted protein evolutionary studies to infer functional domains.

Main Results:

• The active 37LRP/p40 gene consists of 7 exons and 6 introns.
• It exhibits characteristics of a ribosomal protein gene, lacking a TATA box and having multiple transcription start sites.
• Regulatory elements in the 5' genomic region, 5' untranslated region, and intron 1 influence gene expression.
• The carboxy-terminal domain is conserved for 67LR biosynthesis, while the central core binds to ribosomes.

Conclusions:

• The first identification of the active 37LRP/p40 gene structure and regulatory sequences is reported.
• This finding is a critical step towards isolating the human gene.
• Understanding this gene's regulation is key to deciphering molecular mechanisms of tumor invasion and metastasis.