title: Mss4 protein is a regulator of stress response and apoptosis.
abstract: Mss4 (mammalian suppressor of Sec4) is an evolutionarily highly conserved protein and shows high sequence and structural similarity to nucleotide exchange factors. Although Mss4 tightly binds a series of exocytic Rab GTPases, it exercises only a low catalytic activity. Therefore Mss4 was proposed to work rather as a chaperone, protecting nucleotide free Rabs from degradation than as a nucleotide exchange factor. Here we provide further evidence for chaperone-like properties of Mss4. We show that expression levels of cellular Mss4 mRNA and protein are rapidly changed in response to a broad range of extracellular stress stimuli. The alterations are regulated mostly via the (c-jun NH(2)-terminal kinase) JNK stress MAPK signaling pathway and the mode of regulation resembles that of heat shock proteins. Similar to heat shock proteins, upregulation of Mss4 after stress stimulation functions protectively against the programmed cell death. Molecular analysis of the Mss4-mediated inhibition of apoptosis showed that interaction of Mss4 with eIF3f (eukaryotic translation initiation factor 3 subunit f), a member of the translation initiation complex and a protein with distinct pro-apoptotic properties, is the critical event in the anti-apoptotic action of Mss4.
authors.affiliation: Institute of Molecular Virology (IMV), Centre of Molecular Biology of Inflammation (ZMBE), Muenster University Hospital, Von-Esmarch-Str. 56, D-48149 Muenster, Germany.
authors.forename: B M
authors.initials: BM
authors.lastname: Walter
authors.forename: C
authors.initials: C
authors.lastname: Nordhoff
authors.forename: G
authors.initials: G
authors.lastname: Varga
authors.forename: G
authors.initials: G
authors.lastname: Goncharenko
authors.forename: S W
authors.initials: SW
authors.lastname: Schneider
authors.forename: S
authors.initials: S
authors.lastname: Ludwig
authors.forename: V
authors.initials: V
authors.lastname: Wixler
mesh_terms: D017209:Apoptosis; D004268:DNA-Binding Proteins / Q000378:metabolism; D039621:Eukaryotic Initiation Factor-3 / Q000378:metabolism; D020662:Guanine Nucleotide Exchange Factors; D006367:HeLa Cells; D000076249:Heat Shock Transcription Factors; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D020935:MAP Kinase Signaling System; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012333:RNA, Messenger / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism; D020691:rab GTP-Binding Proteins / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D039621:Eukaryotic Initiation Factor-3; D020662:Guanine Nucleotide Exchange Factors; D000076249:Heat Shock Transcription Factors; D018832:Molecular Chaperones; C489794:RABIF protein, human; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D020691:rab GTP-Binding Proteins