These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Characterization of an intramolecular protein-protein interaction in c-Ets1 and its viral homologue v-Ets.
    Author: Schmidt M, Schmidt AM, Dietl J, Kammerer U.
    Journal: Oncol Rep; 2007 Aug; 18(2):457-63. PubMed ID: 17611671.
    Abstract:
    The proto-oncoprotein c-Ets1 is a well-known transcription factor that belongs to the Ets family and plays a role in haematopoietic differentiation, angiogenesis, and carcinogenesis. Ets family members share a unique DNA binding domain, the Ets domain, and are known to control DNA binding activity and transcriptional activation by autoinhibition. In c-Ets1 the DNA binding domain as well as N-terminal and C-terminal inhibitory domains are involved in autoinhibitory regulation. It has been proposed that intramolecular interactions are part of the autoinhibitory mechanism. We applied a GST pull-down assay as well as a two-hybrid system in yeast to show an interaction between the DNA binding domain of c-Ets1 and a domain N-terminal thereof. We have mapped the interaction sites within both of the c-Ets1 domains. Comparison of the analogous intramolecular interaction in c-Ets1 and in v-Ets revealed that the interaction we detected is stronger in v-Ets than in c-Ets1. In view of previous findings from DNA binding studies, and kinetic experiments as well as structural data, our results suggest a new model as to how intramolecular interactions might participate in the regulation of DNA binding. Binding of c-Ets1 to DNA temporarily changes the intramolecular pattern of interaction in c-Ets1, leading to an increase in affinity of c-Ets1 to DNA. In full-length c-Ets1 the intramolecular interactions re-form spontaneously and the protein-DNA complex dissociates. The interaction we characterize herein might increase the DNA binding affinity temporarily in DNA-bound c-Ets1. In v-Ets in which the C-terminal domain is mutated this interaction appears to lead to strong DNA binding affinity. Therefore, changes in v-Ets might contribute to the tumorigenic process by altering intramolecular interactions.
    [Abstract] [Full Text] [Related] [New Search]