Abstract：
:The liver is capable of completely regenerating itself in response to injury and after partial hepatectomy. In liver of old animals, the proliferative response is dramatically reduced, the mechanism for which is unknown. The liver specific protein, C/EBPalpha, normally arrests proliferation of hepatocytes through inhibiting cyclin dependent kinases (cdks). We present evidence that aging switches the liver-specific pathway of C/EBPalpha growth arrest to repression of E2F transcription. We identified an age-specific C/EBPalpha-Rb-E2F4 complex that binds to E2F-dependent promoters and represses these genes. The C/EBPalpha-Rb-E2F4 complex occupies the c-myc promoter and blocks induction of c-myc in livers of old animals after partial hepatectomy. Our results show that the age-dependent switch from cdk inhibition to repression of E2F transcription causes a loss of proliferative response in the liver because of an inability to induce E2F target genes after partial hepatectomy providing a possible mechanism for the age-dependent loss of liver regenerative capacity.
journal_name
Celljournal_title
Cellauthors
Iakova P,Awad SS,Timchenko NAdoi
10.1016/s0092-8674(03)00318-0subject
Has Abstractpub_date
2003-05-16 00:00:00pages
495-506issue
4eissn
0092-8674issn
1097-4172pii
S0092867403003180journal_volume
113pub_type
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