Biomedical subjects

Arndt Benecke

Publications and source records attributed to Arndt Benecke.

4 recordsLinked to original sources

PubMed2002

TIF2 mediates the synergy between RARalpha 1 activation functions AF-1 and AF-2.

Nuclear receptors recruit coregulator complexes through both their AF-1 and AF-2 activation domains. Here we demonstrate that TIF2, a p160 coactivator, is able to bridge the two activation domains of the retinoic acid (RA) receptor isotype RARalpha1, resulting in synergistic activation of transcription. Bridging requires the presence of motifs in region A of RARalpha1 and in the activation domain AD1 of TIF2. Notably, only RARalpha1 exerted this interaction, which requires additional unknown factors. This is the first observation of a RAR isotype-selective coactivator interaction. Because another p160 coactivator, SRC-1, has no effect, this is also the first demonstration of a difference between the members of this coactivator family.

Animals↗

PubMed2002

ADA3-containing complexes associate with estrogen receptor alpha.

Transcriptional repression and activation by nuclear receptors (NRs) are brought about by coregulator complexes. These complexes modify the chromatin environment of target genes and affect the activity of the basal transcription machinery. We have previously implicated the yeast ADA3 protein in transcriptional activation by estrogen and retinoid X receptors in yeast and mammalian cells. Here we report the cloning of the mouse homolog of ADA3 and its characterization with respect to the estrogen receptor alpha (ERalpha) function. Mouse mADA3 is 23% identical and 47% similar to yeast yADA3, and mADA3 in contrast to yADA3 does not interact with NRs directly even though it contains two LxxLL NR boxes. However, the ADA3-containing TBP-free-TAF-containing complex (TFTC) can interact with ERalpha in a ligand-independent manner, indicating that other subunits of the complex are sufficient to mediate interaction with NRs.

Animals↗

PubMed2002

Association of CBP/p300 acetylase and thymine DNA glycosylase links DNA repair and transcription.

DNA repair in chromatin is subject to topological constraints, suggesting a requirement for chromatin modification and remodeling activities. Thymine DNA glycosylase (TDG) initiates repair of G/T and G/U mismatches, commonly associated with CpG islands, by removing thymine and uracil moieties. We report that TDG associates with transcriptional coactivators CBP and p300 and that the resulting complexes are competent for both the excision step of repair and histone acetylation. Furthermore, TDG stimulates CBP transcriptional activity in transfected cells and reciprocally serves as a substrate for CBP/p300 acetylation. Remarkably, this acetylation triggers release of CBP from DNA ternary complexes and also regulates recruitment of repair endonuclease APE. These observations reveal a potential regulatory role for protein acetylation in base mismatch repair and a role for CBP/p300 in maintaining genomic stability.

Acetylation↗

PubMed2002

Hyperstructures, genome analysis and I-cells.

New concepts may prove necessary to profit from the avalanche of sequence data on the genome, transcriptome, proteome and interactome and to relate this information to cell physiology. Here, we focus on the concept of large activity-based structures, or hyperstructures, in which a variety of types of molecules are brought together to perform a function. We review the evidence for the existence of hyperstructures responsible for the initiation of DNA replication, the sequestration of newly replicated origins of replication, cell division and for metabolism. The processes responsible for hyperstructure formation include changes in enzyme affinities due to metabolite-induction, lipid-protein affinities, elevated local concentrations of proteins and their binding sites on DNA and RNA, and transertion. Experimental techniques exist that can be used to study hyperstructures and we review some of the ones less familiar to biologists. Finally, we speculate on how a variety of in silico approaches involving cellular automata and multi-agent systems could be combined to develop new concepts in the form of an Integrated cell (I-cell) which would undergo selection for growth and survival in a world of artificial microbiology.

Algorithms↗