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 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.