Open AccessThe Proline-Histidine-Rich CDK2/CDK4 Interaction Region of C/EBPα Is Dispensable for C/EBPα-Mediated Growth Regulation In Vivo
Author(s) -
Bo T. Porse,
Thomas Åskov Pedersen,
Marie Sigurd Hasemann,
Mikkel Bruhn Schuster,
Peggy Kirstetter,
Tom Luedde,
Inge Damgaard,
Elke Kurz,
Charlotte Karlskov Schjerling,
Claus Nerlov
Publication year - 2006
Publication title -
molecular and cellular biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.14
H-Index - 327
eISSN - 1067-8824
pISSN - 0270-7306
DOI - 10.1128/mcb.26.3.1028-1037.2006
Subject(s) - biology , cell growth , microbiology and biotechnology , cebpa , cell cycle , cyclin dependent kinase 2 , transcription factor , biochemistry , cell , gene
The C/EBPalpha transcription factor regulates growth and differentiation of several tissues during embryonic development. Several hypotheses as to how C/EBPalpha inhibits cellular growth in vivo have been derived, mainly from studies of tissue culture cells. In fetal liver it has been proposed that a short, centrally located, 15-amino-acid proline-histidine-rich region (PHR) of C/EBPalpha is responsible for the growth-inhibitory function of the protein through its ability to interact with CDK2 and CDK4, thereby inhibiting their activities. Homozygous Cebpa(DeltaPHR/DeltaPHR) (DeltaPHR) mice, carrying a modified cebpa allele lacking amino acids 180 to 194, were born at the Mendelian ratio, reached adulthood, and displayed no apparent adverse phenotypes. When fetal livers from the DeltaPHR mice were analyzed for their expression of cell cycle markers, bromodeoxyuridine incorporation, cyclin-dependent kinase 2 kinase activity, and global gene expression, we failed to detect any cell cycle or developmental differences between the DeltaPHR mice and their control littermates. These in vivo data demonstrate that any C/EBPalpha-mediated growth repression via the PHR as well as the basic region is dispensable for proper embryonic development of, and cell cycle control in, the liver. Surprisingly, control experiments performed in C/EBPalpha null fetal livers yielded similar results.