Abstract:
:In mammals, a cell's decision to divide is thought to be under the control of the Rb/E2F pathway. We previously found that inactivation of the Rb family of cell cycle inhibitors (Rb, p107, and p130) in quiescent liver progenitors leads to uncontrolled division and cancer initiation. Here, we show that, in contrast, deletion of the entire Rb gene family in mature hepatocytes is not sufficient for their long-term proliferation. The cell cycle block in Rb family mutant hepatocytes is independent of the Arf/p53/p21 checkpoint but can be abrogated upon decreasing liver size. At the molecular level, we identify YAP, a transcriptional regulator involved in organ size control, as a factor required for the sustained expression of cell cycle genes in hepatocytes. These experiments identify a higher level of regulation of the cell cycle in vivo in which signals regulating organ size are dominant regulators of the core cell cycle machinery.
journal_name
Cell Repjournal_title
Cell reportsauthors
Ehmer U,Zmoos AF,Auerbach RK,Vaka D,Butte AJ,Kay MA,Sage Jdoi
10.1016/j.celrep.2014.06.025subject
Has Abstractpub_date
2014-07-24 00:00:00pages
371-81issue
2issn
2211-1247pii
S2211-1247(14)00494-Xjournal_volume
8pub_type
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