Loss of Survivin influences liver regeneration and is associated with impaired Aurora B function View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2013-03-22

AUTHORS

S Hagemann, J Wohlschlaeger, S Bertram, B Levkau, A Musacchio, E M Conway, D Moellmann, G Kneiseler, G Pless-Petig, K Lorenz, B Sitek, H A Baba

ABSTRACT

The chromosomal passenger complex (CPC) acts as a key regulator of mitosis, preventing asymmetric segregation of chromosomal material into daughter cells. The CPC is composed of three non-enzymatic components termed Survivin, the inner centromere protein (INCENP) and Borealin, and an enzymatic component, Aurora B kinase.Survivin is necessary for the appropriate separation of sister chromatids during mitosis and is involved in liver regeneration, but its role in regenerative processes is incompletely elucidated. Whether Survivin, which is classified as an inhibitor of apoptosis protein (IAP) based on domain composition, also has a role in apoptosis is controversial. The present study examined thein vivoeffects of Survivin ablation in the liver and during liver regeneration after 70% hepatectomy in a hepatocyte-specific knockout mouse model. The absence of Survivin caused a reduction in the number of hepatocytes in the liver, together with an increase in cell volume, macronucleation and polyploidy, but no changes in apoptosis. During liver regeneration, mitosis of hepatocytes was associated with mislocalization of the members of the CPC, which were no longer detectable at the centromere despite an unchanged protein amount. Furthermore, the loss of survivin in regenerating hepatocytes was associated with reduced levels of phosphorylated Histone H3 at serine 28 and abolished phosphorylation of CENP-A and Hec1 at serine 55, which is a consequence of decreased Aurora B kinase activity. These data indicate that Survivin expression determines hepatocyte number during liver development and liver regeneration. Lack of Survivin causes mislocalization of the CPC members in combination with reduced Aurora B activity, leading to impaired phosphorylation of its centromeric target proteins and inappropriate cytokinesis. More... »

PAGES

834-844

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/cdd.2013.20

DOI

http://dx.doi.org/10.1038/cdd.2013.20

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1015454792

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/23519077


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86 knockout mouse model
87 lack
88 levels
89 liver
90 liver development
91 liver regeneration
92 loss
93 loss of survivin
94 materials
95 members
96 mislocalization
97 mitosis
98 mitosis of hepatocytes
99 model
100 mouse model
101 non-enzymatic components
102 number
103 number of hepatocytes
104 passenger complex
105 phosphorylated histone H3
106 phosphorylation
107 phosphorylation of CENP
108 polyploidy
109 present study
110 process
111 protein
112 protein amount
113 reduced levels
114 reduction
115 regeneration
116 regenerative processes
117 regulator
118 role
119 segregation
120 separation
121 serine 28
122 serine 55
123 sister chromatids
124 study
125 survivin
126 survivin expression
127 target proteins
128 volume
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