Abstract
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Molecular and Cellular Biology |
| Vol/bind | 26 |
| Udgave nummer | 3 |
| Sider (fra-til) | 1028-37 |
| Antal sider | 9 |
| ISSN | 0270-7306 |
| DOI | |
| Status | Udgivet - 2006 |
Bibliografisk note
Keywords: Adipocytes; Amino Acid Sequence; Animals; CCAAT-Enhancer-Binding Protein-alpha; Cell Differentiation; Cyclin-Dependent Kinase 2; Cyclin-Dependent Kinase 4; Embryo, Mammalian; Embryonic Development; Histidine; Humans; Liver; Mice; Mice, Mutant Strains; Molecular Sequence Data; Proline; Protein Structure, Tertiary; Rats; Sequence DeletionAdgang til dokumentet
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I: Molecular and Cellular Biology, Bind 26, Nr. 3, 2006, s. 1028-37.
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review
}
TY - JOUR
T1 - The proline-histidine-rich CDK2/CDK4 interaction region of C/EBPalpha is dispensable for C/EBPalpha-mediated growth regulation in vivo.
AU - Porse, Bo Torben
AU - Pedersen, Thomas Askov
AU - Hasemann, Marie Sigurd
AU - Schuster, Mikkel Bruhn
AU - Kirstetter, Peggy
AU - Luedde, Tom
AU - Damgaard, Inge
AU - Kurz, Elke
AU - Schjerling, Charlotte Karlskov
AU - Nerlov, Claus
N1 - Keywords: Adipocytes; Amino Acid Sequence; Animals; CCAAT-Enhancer-Binding Protein-alpha; Cell Differentiation; Cyclin-Dependent Kinase 2; Cyclin-Dependent Kinase 4; Embryo, Mammalian; Embryonic Development; Histidine; Humans; Liver; Mice; Mice, Mutant Strains; Molecular Sequence Data; Proline; Protein Structure, Tertiary; Rats; Sequence Deletion
PY - 2006
Y1 - 2006
N2 - 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.
AB - 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.
U2 - 10.1128/MCB.26.3.1028-1037.2006
DO - 10.1128/MCB.26.3.1028-1037.2006
M3 - Journal article
C2 - 16428455
SN - 0270-7306
VL - 26
SP - 1028
EP - 1037
JO - Molecular and Cellular Biology
JF - Molecular and Cellular Biology
IS - 3
ER -