The 37 LRP/P40 polypeptide: a multifunctional pleiotropic molecule involved in tumorigenesis and metastasis. A review

• Published in: Belgian journal of zoology Vol. 127; no. 1
• Main Authors: Clausse, N, Jackers, P, Castronovo, V. (Liege Univ. (Belgium). Metastasis Research Laboratory)
• Format: Journal Article
• Language: English
• Published: 01.06.1997
• Subjects: ADN; CLONACION MOLECULAR; CLONAGE MOLECULAIRE; DNA; GENOMAS; GENOME; GENOMES; MOLECULAR CLONING; NEOPLASMAS; NEOPLASME; NEOPLASMS; PROTEINAS; PROTEINE; PROTEINS; RIBOSOMAS; RIBOSOME; RIBOSOMES
• ISSN: 0777-6276

A cDNA coding for a 37 kDa polypeptide has been the center of major interest since it is consistently up-regulated in several cancers in association with the metastatic phenotype of the lesion. Furthermore, this polypeptide displays intriguing multifunctional properties as it has been cloned both as the metastasis-associated 67 kD membrane-associated laminin receptor precursor (37 LRP) but also as a cytoplasmic ribosomal-associated protein p40. Isolation of the gene coding for the 37 LRP/p40 peptide in humans and birds, analysis of their structures and extensive amino-acid comparison between available species sequences have brought new topological arguments in favor of a multifunctional role for this protein in cells. Indeed, both genes display characteristics of house-keeping genes and in particular of ribosomal protein -encoding genes. Comparison between all 37LRP/p40 amino-acid sequences identifies a particularly well conserved region in the center of the protein in all organisms. This central part of the protein is the only region similar to the parentally linked RS2 prokaryotic ribosomal protein. In contrast, the carboxy terminal end of the protein is highly variable in all organisms until the vertebrates appear. As vertebrates are the only organisms in which a 67 LR molecule has been clearly described, it is suggested that this region of the molecule supports a new function i.e the ability to be included into the 67 kD cell surface laminin receptor. This hypothesis is further sustained by the fact that the carboxy terminal end of the protein is precisely encoded by the last two exons. An evolutionary scenario is proposed in which the 37 LRP/p40 molecule has always had a function as a ribosome-associated protein, encoded by the central highly conserved region. In the course of evolution, an additional function linked to the carboxy terminal end of the protein would have developed in organisms in which cell-matrix interactions became more complex.