title: A mitotically inheritable unit containing a MAP kinase module.
abstract: Prions are novel kinds of hereditary units, relying solely on proteins, that are infectious and inherited in a non-Mendelian fashion. To date, they are either based on autocatalytic modification of a 3D conformation or on autocatalytic cleavage. Here, we provide further evidence that in the filamentous fungus Podospora anserina, a MAP kinase cascade is probably able to self-activate and generate C, a hereditary unit that bears many similarities to prions and triggers cell degeneration. We show that in addition to the MAPKKK gene, both the MAPKK and MAPK genes are necessary for the propagation of C, and that overexpression of MAPK as that of MAPKKK facilitates the appearance of C. We also show that a correlation exists between the presence of C and localization of the MAPK inside nuclei. These data emphasize the resemblance between prions and a self-positively regulated cascade in terms of their transmission. This thus further expands the concept of protein-base inheritance to regulatory networks that have the ability to self-activate.
authors.affiliation: Institut de Génétique et Microbiologie, Unité Mixte de Recherche 8621, Centre National de la Recherche Scientifique, Université de Paris-Sud 11, Bâtiment 400, F-91405 Orsay Cedex, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Kicka
authors.forename: Crystel
authors.initials: C
authors.lastname: Bonnet
authors.forename: Andrew K
authors.initials: AK
authors.lastname: Sobering
authors.forename: Latha P
authors.initials: LP
authors.lastname: Ganesan
authors.forename: Philippe
authors.initials: P
authors.lastname: Silar
mesh_terms: D000483:Alleles; D002467:Cell Nucleus / Q000201:enzymology; D004252:DNA Mutational Analysis; D044127:Epigenesis, Genetic; D005656:Fungal Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D017353:Gene Deletion; D015870:Gene Expression; D005800:Genes, Fungal; D049452:Green Fluorescent Proteins / Q000378:metabolism; D025301:Hyphae / Q000201:enzymology / Q000254:growth & development; D020935:MAP Kinase Signaling System / Q000235:genetics*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000235:genetics / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D008938:Mitosis; D008969:Molecular Sequence Data; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D048468:Podospora / Q000201:enzymology / Q000235:genetics / Q000254:growth & development; D011328:Prions / Q000235:genetics; D019076:Transgenes
chemical_list: D005656:Fungal Proteins; D011328:Prions; D049452:Green Fluorescent Proteins; D019255:NADPH Oxidases; D020928:Mitogen-Activated Protein Kinases; D020929:Mitogen-Activated Protein Kinase Kinases