Actin-Induced Hyperactivation of the Ras Signaling Pathway Leads to Apoptosis in Saccharomyces cerevisiae

Gourlay, Campbell W. and Ayscough, K.R. (2006) Actin-Induced Hyperactivation of the Ras Signaling Pathway Leads to Apoptosis in Saccharomyces cerevisiae. Molecular and Cellular Biology, 26 (17). pp. 6487-6501. (Access to this publication is restricted)

PDF
Restricted to Registered users only
Contact us about this Publication Download (1MB)
[img]
Official URL
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=...

Abstract

Recent research has revealed a conserved role for the actin cytoskeleton in the regulation of aging and apoptosis among eukaryotes. Here we show that the stabilization of the actin cytoskeleton caused by deletion of Sla1p or End3p leads to hyperactivation of the Ras signaling pathway. The consequent rise in cyclic AMP (cAMP) levels leads to the loss of mitochondrial membrane potential, accumulation of reactive oxygen species (ROS), and cell death. We have established a mechanistic link between Ras signaling and actin by demonstrating that ROS production in actin-stabilized cells is dependent on the G-actin binding region of the cyclase-associated protein Srv2p/CAP. Furthermore, the artificial elevation of cAMP directly mimics the apoptotic phenotypes displayed by actin-stabilized cells. The effect of cAMP elevation in inducing actin-mediated apoptosis functions primarily through the Tpk3p subunit of protein kinase A. This pathway represents the first defined link between environmental sensing, actin remodeling, and apoptosis in Saccharomyces cerevisiae.

Item Type: Article
Subjects: Q Science
Divisions: Faculties > Science Technology and Medical Studies > School of Biosciences > Cell & Developmental Biology Group
Depositing User: Sue Davies
Date Deposited: 19 Dec 2007 18:14
Last Modified: 09 Aug 2013 08:06
Resource URI: http://kar.kent.ac.uk/id/eprint/422 (The current URI for this page, for reference purposes)
  • Depositors only (login required):

Downloads

Downloads per month over past year