title: Proteome analysis of a hepatocyte-specific BIRC5 (survivin)-knockout mouse model during liver regeneration.
abstract: The Baculoviral IAP repeat-containing protein 5 (BIRC5), also known as inhibitor of apoptosis protein survivin, is a member of the chromosomal passenger complex and a key player in mitosis. To investigate the function of BIRC5 in liver regeneration, we analyzed a hepatocyte-specific BIRC5-knockout mouse model using a quantitative label-free proteomics approach. Here, we present the analyses of the proteome changes in hepatocyte-specific BIRC5-knockout mice compared to wildtype mice, as well as proteome changes during liver regeneration induced by partial hepatectomy in wildtype mice and mice lacking hepatic BIRC5, respectively. The BIRC5-knockout mice showed an extensive overexpression of proteins related to cellular maintenance, organization and protein synthesis. Key regulators of cell growth, transcription and translation MTOR and STAT1/STAT2 were found to be overexpressed. During liver regeneration proteome changes representing a response to the mitotic stimulus were detected in wildtype mice. Mainly proteins corresponding to proliferation, cell cycle and cytokinesis were up-regulated. The hepatocyte-specific BIRC5-knockout mice showed impaired liver regeneration, which had severe consequences on the proteome level. However, several proteins with function in mitosis were found to be up-regulated upon the proliferative stimulus. Our results show that the E3 ubiquitin-protein ligase UHRF1 is strongly up-regulated during liver regeneration independently of BIRC5.
authors.affiliation: Medizinisches Proteom-Center, Ruhr Universität Bochum , Bochum, Germany.
authors.forename: Thilo
authors.initials: T
authors.lastname: Bracht
authors.forename: Sascha
authors.initials: S
authors.lastname: Hagemann
authors.forename: Marius
authors.initials: M
authors.lastname: Loscha
authors.forename: Dominik A
authors.initials: DA
authors.lastname: Megger
authors.forename: Juliet
authors.initials: J
authors.lastname: Padden
authors.forename: Martin
authors.initials: M
authors.lastname: Eisenacher
authors.forename: Katja
authors.initials: K
authors.lastname: Kuhlmann
authors.forename: Helmut E
authors.initials: HE
authors.lastname: Meyer
authors.forename: Hideo A
authors.initials: HA
authors.lastname: Baba
authors.forename: Barbara
authors.initials: B
authors.lastname: Sitek
mesh_terms: D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins; D015870:Gene Expression; D055786:Gene Knockout Techniques; D022781:Hepatocytes / Q000378:metabolism*; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics*; D008099:Liver / Q000166:cytology / Q000502:physiology; D008115:Liver Regeneration; D018345:Mice, Knockout; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D020543:Proteome / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics*; D000077022:Survivin; D044767:Ubiquitin-Protein Ligases; D015854:Up-Regulation
chemical_list: C117749:Birc5 protein, mouse; D022762:CCAAT-Enhancer-Binding Proteins; D051034:Inhibitor of Apoptosis Proteins; D009687:Nuclear Proteins; D020543:Proteome; D012097:Repressor Proteins; D000077022:Survivin; D044767:Ubiquitin-Protein Ligases; C117054:Uhrf1 protein, mouse