title: Protein chimerism: novel source of protein diversity in humans adds complexity to bottom-up proteomics.
abstract: Three main molecular mechanisms are considered to contribute expanding the repertoire and diversity of proteins present in living organisms: first, at DNA level (gene polymorphisms and single nucleotide polymorphisms); second, at messenger RNA (pre-mRNA and mRNA) level including alternative splicing (also termed differential splicing or cis-splicing); finally, at the protein level mainly driven through PTM and specific proteolytic cleavages. Chimeric mRNAs constitute an alternative source of protein diversity, which can be generated either by chromosomal translocations or by trans-splicing events. The occurrence of chimeric mRNAs and proteins is a frequent event in cells from the immune system and cancer cells, mainly as a consequence of gene rearrangements. Recent reports support that chimeric proteins may also be expressed at low levels under normal physiological circumstances, thus, representing a novel source of protein diversity. Notably, recent publications demonstrate that chimeric protein products can be successfully identified through bottom-up proteomic analyses. Several questions remain unsolved, such as the physiological role and impact of such chimeric proteins or the potential occurrence of chimeric proteins in higher eukaryotic organisms different from humans. The occurrence of chimeric proteins certainly seems to be another unforeseen source of complexity for the proteome. It may be a process to take in mind not only when performing bottom-up proteomic analyses in cancer studies but also in general bottom-up proteomics experiments.
authors.affiliation: Centro Nacional de Biotecnología, Lab 115, Dpt. Biología Molecular y Celular, Spanish National Research Council, Madrid, Spain. jcasado@cnb.csic.es
authors.forename: Juan
authors.initials: J
authors.lastname: Casado-Vela
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Lacal
authors.forename: Felix
authors.initials: F
authors.lastname: Elortza
mesh_terms: D016044:Fusion Proteins, bcr-abl / Q000145:classification / Q000235:genetics; D014644:Genetic Variation; D006801:Humans; D050506:Mutant Chimeric Proteins / Q000737:chemistry / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D040901:Proteomics; D012322:RNA Precursors / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics
chemical_list: D050506:Mutant Chimeric Proteins; D011506:Proteins; D012322:RNA Precursors; D012333:RNA, Messenger; D016044:Fusion Proteins, bcr-abl