Visit our Expo - Redox and Inflammation signaling 2012

Session XIV : Transcriptional and translational control Poster XIV, 18
Transcriptional regulation of cell proliferation signalling pathways by the transcription
factor E2F2 during liver regeneration
Igotz Delgado, Yuri Rueda, Olatz Fresnedo and Begoña Ochoa.
Department of Physiology, University of the Basque Country Medical School, PO Box
699, Bilbao, Spain. E-mail: igotzdelgado@yahoo.es
E2F transcription factors are key regulators of cell cycle progression; they are fundamental
for crossing the G1/S checkpoint as they regulate the expression of genes required for DNA
replication. During the G1 phase, pocket proteins such as pRb (retinoblastoma protein) are
blocking E2Fs activity. Cyclin dependent kinases phosphorylate pRbs so that E2Fs are
released. When associated with pRb family members, the E2Fs function as transcriptional
repressors, whereas free E2F activates transcription. The pRb-E2F pathway is a downstream
target of mitogenic signalling pathways. E2F2 transcription factors are activator members of
E2F family as they induce cell cycle entry in quiescent cells. Liver regeneration is considered
an appropriate model to analyse factors related to cell cycle because, following an hepatic
tissue resection, 95% of hepatic cells (which normally stay quiescent) enter cell cycle to start
regeneration while maintaining their metabolic functions. We have addressed the role of E2F2
in liver regeneration using the well characterised paradigm of 70% partial hepatectomy (PH)
in wild-type and E2F2-/- mice and high-density oligonucleotide arrays to identify genes in
which the change in expression in response to hepatectomy differed. Measurements were
performed at 48 hours post-hepatectomy, as hepatocyte replication peaked at this time in the
regenerating mouse. E2F2-/- mice exhibited a delayed liver regeneration, showing the
importance of this transcription factor in the regenerative process. The microarray analysis
showed that genes belonging to antiproliferative signaling pathways such as Rras, dual
specific phosphatases 6 and 16 or Map kinase-activated protein kinase 2 were upregulated in
E2F2-/- mice during the regenerative process, this explaining, at least in fact, that liver
regeneration is retarded in the absence of E2F2. In conclusion, regardless of its action on
proliferation, the transcription factor E2F2 enhances the expression of some genes involved in
antiproliferative signalling pathways of the liver.
Supported by the Basque Government (Etortek02, IE019)
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