Proteome Analysis of a Hepatocyte-Specific BIRC5 (Survivin)-Knockout Mouse Model during Liver Regeneration

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 m...

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Bibliographic Details
Published in:Journal of proteome research 2014-06, Vol.13 (6), p.2771-2782
Main Authors: Bracht, Thilo, Hagemann, Sascha, Loscha, Marius, Megger, Dominik A, Padden, Juliet, Eisenacher, Martin, Kuhlmann, Katja, Meyer, Helmut E, Baba, Hideo A, Sitek, Barbara
Format: Article
Language:English
Subjects:
Animals
Gene Expression
Gene Knockout Techniques
Hepatocytes - metabolism
Inhibitor of Apoptosis Proteins - genetics
Liver - cytology
Liver - physiology
Liver Regeneration
Mice, Knockout
Nuclear Proteins - genetics
Nuclear Proteins - metabolism
Proteome - genetics
Proteome - metabolism
Repressor Proteins - genetics
Up-Regulation
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Summary: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.
ISSN:1535-3893
1535-3907
DOI:10.1021/pr401188r