1: Mol Cell Biol. 1999 Nov;19(11):7529-38. 

The yeast ras/cyclic AMP pathway induces invasive growth by suppressing the
cellular stress response.

Stanhill A, Schick N, Engelberg D.

Department of Biological Chemistry, The Institute of Life Sciences, The Hebrew
University of Jerusalem, Jerusalem 91904, Israel.

Haploid yeast cells are capable of invading agar when grown on rich media. Cells
of the Sigma1278b genetic background manifest this property, whereas other
laboratory strains are incapable of invasive growth. We show that disruption of
the RAS2 gene in the Sigma1278b background significantly reduces invasive growth
but that expression of a constitutively active Ras2p (Ras2(Val19)p) in this
strain has a minimal effect on its invasiveness. On the other hand, expression
of Ras2(Val19)p in another laboratory strain, SP1, rendered it invasive. These
results suggest that a hyperactive Ras2 pathway induces invasive growth and that
this pathway might be overactive in the Sigma1278b genetic background. Indeed,
cells of the Sigma1278b are defective in the induction of stress-responsive
genes, while their Gcn4 target genes are constitutively transcribed. This
pattern of gene expression was previously shown to be associated with an active
Ras/cyclic AMP (cAMP) pathway. We show that suppression of stress-related genes
in Sigma1278b cells is a result of their inability to activate transcription
through the stress response element (STRE). Disruption of RAS2, which abolished
invasiveness, induced an increase in STRE activity. Further, in the SP1 genetic
background, disruption of either the MSN2/4 genes (encoding activators of STRE)
or the yAP-1 gene was sufficient to restore invasive growth in ras2Delta cells.
We conclude that Ras2-mediated suppression of the stress response is sufficient
to induce invasiveness. Accordingly, the fact that the stress response is
suppressed in Sigma1278b background explains its invasiveness. It seems that
invasiveness is a phenotype related to unregulated growth and is therefore
manifested by cells harboring an overactive Ras/cAMP cascade. In this respect,
invasiveness in yeast is reminiscent of the property of ras-transformed
fibroblasts to invade soft agar.

PMID: 10523641 [PubMed - indexed for MEDLINE]


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