Cold Spring Harbor Laboratory

About: Cold Spring Harbor Laboratory is a nonprofit organization based out in Cold Spring Harbor, New York, United States. It is known for research contribution in the topics: Gene & Genome. The organization has 3772 authors who have published 6603 publications receiving 1010873 citations. The organization is also known as: CSHL.

Direct coupling of the cell cycle and cell death machinery by E2F.

Abstract: Unrestrained E2F activity forces S phase entry and promotes apoptosis through p53-dependent and -independent mechanisms. Here, we show that deregulation of E2F by adenovirus E1A, loss of Rb or enforced E2F-1 expression results in the accumulation of caspase proenzymes through a direct transcriptional mechanism. Increased caspase levels seem to potentiate cell death in the presence of p53-generated signals that trigger caspase activation. Our results demonstrate that mitogenic oncogenes engage a tumour suppressor network that functions at multiple levels to efficiently induce cell death. The data also underscore how cell cycle progression can be coupled to the apoptotic machinery.

Destruction of Myc by ubiquitin‐mediated proteolysis: cancer‐associated and transforming mutations stabilize Myc

Abstract: The human proto-oncogene c-myc encodes a highly unstable transcription factor that promotes cell proliferation. Although the extreme instability of Myc plays an important role in preventing its accumulation in normal cells, little is known about how Myc is targeted for rapid destruction. Here, we have investigated mechanisms regulating the stability of Myc. We show that Myc is destroyed by ubiquitin-mediated proteolysis, and define two elements in Myc that oppositely regulate its stability: a transcriptional activation domain that promotes Myc destruction, and a region required for association with the POZ domain protein Miz-1 that stabilizes Myc. We also show that Myc is stabilized by cancer-associated and transforming mutations within its transcriptional activation domain. Our data reveal a complex network of interactions regulating Myc destruction, and imply that enhanced protein stability contributes to oncogenic transformation by mutant Myc proteins.

Yeast origin recognition complex functions in transcription silencing and DNA replication

Abstract: The genes encoding two of the subunits of the Saccharomyces cerevisiae origin recognition complex (ORC) have been isolated. Characterization of a temperature-sensitive mutation in the gene encoding the 72-kD subunit of ORC (ORC2) indicates that this protein complex functions early in the DNA replication process. Moreover, ORC derived from orc2ts cells is defective for DNA binding. Others have shown a defect in orc2ts cells in transcriptional silencing at the silent mating-type loci. Consistent with this finding, ORC specifically binds to each of the four mating-type silencers identified in yeast. These findings support the hypothesis that ORC acts as an initiator protein at yeast origins of DNA replication and suggest that ORC also functions in the determination of transcriptional domains.