title: The familial mediterranean fever protein interacts and colocalizes with a putative Golgi transporter.
abstract: The biological function of pyrin, the protein mutated in Familial Mediterranean Fever (FMF), has not been elucidated. Based on sequence homology, a transcription factor activity was proposed for this neutrophil-specific protein. In a yeast two-hybrid assay, neither transcription activation activity nor any self interaction was detected for pyrin. Screening of an expression cDNA library of peripheral blood leukocytes using as bait the carboxyl portion of pyrin (amino acids 557-781), which contains most of the FMF mutations, led to the identification of P/M-IP1 (pyrin/marenostrin interacting protein 1). A splice variant of P/M-IP1, GTC-90, had previously been described as a component of the 13S hetero-oligomeric protein complex that stimulates in vitro Golgi transport. We have now shown that P/M-IP1 colocalizes with pyrin in the perinuclear cytoplasm of Cos-7 cells and that the interaction between these two proteins is impaired by FMF causing mutations in pyrin. These data suggest that, at some stage of its functional pathway, pyrin resides in the cytoplasm and might be involved in, or impacted by, cellular protein sorting by the Golgi apparatus. The data also imply that P/M-IP1 may be involved in the abnormal inflammatory response that occurs in patients with FMF.
authors.affiliation: Ahmanson Department of Pediatrics, Steven Spielberg Pediatric Research Center, Medical Genetics Birth Defects Center, and Department of Medicine, Cedars-Sinai Medical Center and UCLA School of Medicine, Los Angeles, California 90048, USA.
authors.forename: X
authors.initials: X
authors.lastname: Chen
authors.forename: Y
authors.initials: Y
authors.lastname: Bykhovskaya
authors.forename: N
authors.initials: N
authors.lastname: Tidow
authors.forename: M
authors.initials: M
authors.lastname: Hamon
authors.forename: Z
authors.initials: Z
authors.lastname: Bercovitz
authors.forename: O
authors.initials: O
authors.lastname: Spirina
authors.forename: N
authors.initials: N
authors.lastname: Fischel-Ghodsian
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport; D017398:Alternative Splicing; D000818:Animals; D015152:Blotting, Northern; D019556:COS Cells; D002352:Carrier Proteins / Q000378:metabolism*; D003598:Cytoskeletal Proteins; D010505:Familial Mediterranean Fever / Q000378:metabolism*; D006056:Golgi Apparatus / Q000378:metabolism*; D006098:Granulocytes / Q000378:metabolism; D008565:Membrane Proteins; D009154:Mutation; D020033:Protein Isoforms / Q000378:metabolism; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D000071198:Pyrin; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000378:metabolism*; D020798:Two-Hybrid System Techniques
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; C115632:COG5 protein, human; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; C000604192:MEFV protein, human; D008565:Membrane Proteins; D020033:Protein Isoforms; D011506:Proteins; D000071198:Pyrin; D014157:Transcription Factors