Expression of the HTLV-I Tax Transactivator in Yeast: Correlation Between Phenotypic Alterations and Tax Function in Higher Eukaryotes

Abstract

The transcriptional activator protein (Tax) from human T-cell leukemia virus type 1 was expressed in yeast using several different promoters in several strains: In all instances, expression of Tax resulted in very strong aggregation of the yeast cells. This phenotype appears to be identical by all criteria tested to the flocculation phenotype of the dominant mutation flo 1. Of most significance, mutations in Tax that affect transactivation of the IL-2R alpha regulatory sequences, but retain their ability to activate the viral long terminal repeat also fail to yield the aggregation phenotype. Based on these findings, expression of Tax in yeast may prove to be a simple primordial system for examining the regulatory mechanisms and cellular functions involved in regulation of gene expression.

Yeast flocculation: Reconciliation of physiological and genetic viewpoints

“…Similarly, disruption of the casein kinase I1 gene, CKA2, also results in flocculation (Padmanabha et al, 1990) prior to cell death. Finally, flocculation identical to that of FLOl gene-containing strains, has been reported in strains transformed with the HTLV-I Tax transactivator (Kramer et al, 1990). Expression of this viral transcriptional activator protein caused strong flocculation, irrespective of the promoters employed.…”

“…However, this simple model is clearly incorrect since non-flocculent cells have been shown to flocculate following mutation at various loci, such as tupl or cyc8. The phenotypes of these strains, flocculent by mutation, are identical to that of FLOl gene-containing strains (Lipke and Hull-Pillsbury, 1984;Kramer et al, 1990;Stratford and Assinder, 199 1). Since these mutations obviously cannot generate de novo lectin genes, silent Iectin genes must have been present in these strains prior to mutation, whether as suppressed alleles at any of the FLO loci, or elsewhere.…”

“…This is supported by recent work by Williams and Trumbly (1990), who suggested that TUPl and CYC8 inhibit a class of transcriptional activators in their regulation of catabolite repression. Finally, the proposal that FLU genes are regulatory activators is strongly supported by the fortuitous discovery that flocculation in yeast, identical to that of FLOI, can be induced by expression of viral regulatory activators (Kramer et al, 1990).…”

“…Furthermore, the mechanism of transport of viral proteins to the cell surface (Bergmann et al,198 1) is identical to that proposed for secretion of yeast lectins. Finally, the theory of viral involvement with flocculation is supported by the recent discovery that yeast flocculation may be induced by expression of viral transactivator proteins in yeast (Kramer et al, 1990). Viral activators are perhaps more likely to stimulate activity of viral-related genes in yeast.…”

Population dynamics of flocculating yeasts

“…These mutations and their pleiotropic effects are listed by Stratford [60]. In the case of mutation in TUPI and CYC8 loci, cells exhibit calcium-dependent flocculation [61,62].…”