Biomedical subjects

Bo Torben Porse

Publications and source records attributed to Bo Torben Porse.

4 recordsLinked to original sources

PubMed2006

C/EBPalpha: a tumour suppressor in multiple tissues?

The CCATT/enhancer binding protein alpha, C/EBPalpha, is a key transcription factor involved in late differentiation events of several cell types. Besides acting as a classical transcription factor, C/EBPalpha is also a well-characterized inhibitor of mitotic growth in most cell lines tested. In line with its anti-mitotic properties, C/EBPalpha has been shown to interact with, and alter the activities of, several cell cycle related proteins and a number of models as to the mechanistics of C/EBPalpha-mediated growth repression have been proposed. More recently, several reports have indicated that C/EBPalpha acts as a tumour suppressor in the hematopoietic system and that mutation within C/EBPalpha is sufficient to induce tumourigenesis. Here, we will review these data and probe the possibility that C/EBPalpha also act as a tumour suppressor in other C/EBPalpha-expressing tissues.

Animals↗

PubMed2006

The proline-histidine-rich CDK2/CDK4 interaction region of C/EBPalpha is dispensable for C/EBPalpha-mediated growth regulation in vivo.

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.

Adipocytes↗

PubMed2004

A novel partial modification at C2501 in Escherichia coli 23S ribosomal RNA.

Escherichia coli is the best-characterized organism with respect to posttranscriptional modifications of its ribosomal RNA (rRNA). It is presently believed that all the modified nucleotides have been identified, primarily on the basis of two detection methods; modification-induced inhibition of the enzyme reverse transcriptase or analysis by combined HPLC and electrospray ionization mass spectrometry. Comparison of data from these different approaches reveals a disagreement regarding modification of C2501 in E. coli 23S rRNA. A. Bakin and J. Ofengand previously reported the detection of a modification at this site based on a reverse transcriptase assay. J.A. McCloskey and coworkers could not confirm the existence of such a modification using an electrospray ionization mass spectrometry approach. C2501 is therefore generally considered unmodified. We have used a strategy involving isolation of a specific rRNA fragment from E. coli 23S rRNA followed by Matrix Assisted Laser Desorption/Ionization mass spectrometry and tandem mass spectrometry to investigate this controversy. Our data reveal a novel 16-Da partial modification at C2501. We believe that the data reported here clarify the above discrepancy, because a minor partial modification detected in a reverse transcriptase assay would not necessarily be detected by the original mass spectrometry approach. The level of modification was furthermore monitored in different growth situations, and we found a significant positive regulation in stationary phase cells. C2501 is universally conserved and implicated in structure folds very close to the catalytic center of the ribosome. Moreover, several antibiotics bind to nucleotides in this region, which altogether make a modification at this site interesting.

Base Sequence↗

PubMed2003

[Transgenic mice as disease models].

Transgenic animal models have proven to be useful tools in understanding both basic biology and the events associated with disease. Recent technical advances in the area of genomic manipulation in combination with the availability of the human and murine genomic sequences now allow the precise tailoring of the mouse genome. In this review we describe a few systems in which transgenic animal models have been employed for the purpose of studying the etiology of human diseases.

Animals↗