Tra1 is an essential component of the SAGA/SLIK and NuA4 complexes in S. cerevisiae, recruiting these co-activator complexes to specific promoters. As a PIKK family member, Tra1 is characterized by a C-terminal phosphoinositide 3-kinase (PI3K) domain. Unlike other PIKK family members (e.g., Tor1, Tor2, Mec1, Tel1), Tra1 has no demonstrable kinase activity. We identified three conserved arginine residues in Tra1 that reside proximal or within the cleft between the N- and C-terminal subdomains of the PI3K domain. To establish a function for Tra1's PI3K domain and specifically the cleft region, we characterized a tra1 allele where these three arginine residues are mutated to glutamine. The half-life of the Tra1Q3 protein is reduced but its steady state level is maintained at near wild-type levels by a transcriptional feedback mechanism. The tra1Q3 allele results in slow growth under stress and alters the expression of genes also regulated by other components of the SAGA complex. Tra1Q3 is less efficiently transported to the nucleus than the wild-type protein. Likely related to this, Tra1Q3 associates poorly with SAGA/SLIK and NuA4. The ratio of Spt7(SLIK) to Spt7(SAGA) increases in the tra1Q3 strain and truncated forms of Spt20 become apparent upon isolation of SAGA/SLIK. Intragenic suppressor mutations of tra1Q3 map to the cleft region further emphasizing its importance. We propose that the PI3K domain of Tra1 is directly or indirectly important for incorporating Tra1 into SAGA and NuA4 and thus the biosynthesis and/or stability of the intact complexes.
机构:
Univ Western Ontario, Dept Biochem, Schulich Sch Med & Dent, London, ON N6A 5C1, CanadaUniv Western Ontario, Dept Biochem, Schulich Sch Med & Dent, London, ON N6A 5C1, Canada
Genereaux, Julie
;
Kvas, Stephanie
论文数: 0引用数: 0
h-index: 0
机构:
Univ Western Ontario, Dept Biochem, Schulich Sch Med & Dent, London, ON N6A 5C1, CanadaUniv Western Ontario, Dept Biochem, Schulich Sch Med & Dent, London, ON N6A 5C1, Canada
Kvas, Stephanie
;
Dobransky, Dominik
论文数: 0引用数: 0
h-index: 0
机构:
Univ Western Ontario, Dept Biochem, Schulich Sch Med & Dent, London, ON N6A 5C1, CanadaUniv Western Ontario, Dept Biochem, Schulich Sch Med & Dent, London, ON N6A 5C1, Canada
Dobransky, Dominik
;
Karagiannis, Jim
论文数: 0引用数: 0
h-index: 0
机构:
Univ Western Ontario, Dept Biol, London, ON N6A 5B7, CanadaUniv Western Ontario, Dept Biochem, Schulich Sch Med & Dent, London, ON N6A 5C1, Canada
Karagiannis, Jim
;
Gloor, Gregory B.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Western Ontario, Dept Biochem, Schulich Sch Med & Dent, London, ON N6A 5C1, CanadaUniv Western Ontario, Dept Biochem, Schulich Sch Med & Dent, London, ON N6A 5C1, Canada
Gloor, Gregory B.
;
Brandl, Christopher J.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Western Ontario, Dept Biochem, Schulich Sch Med & Dent, London, ON N6A 5C1, CanadaUniv Western Ontario, Dept Biochem, Schulich Sch Med & Dent, London, ON N6A 5C1, Canada
机构:
Fred Hutchinson Canc Res Ctr, Div Basic Sci, Seattle, WA 98104 USA
Univ Washington, Biol Phys Struct & Design Program, Seattle, WA 98195 USAFred Hutchinson Canc Res Ctr, Div Basic Sci, Seattle, WA 98104 USA
Han, Yan
;
Luo, Jie
论文数: 0引用数: 0
h-index: 0
机构:
Inst Syst Biol, Seattle, WA USAFred Hutchinson Canc Res Ctr, Div Basic Sci, Seattle, WA 98104 USA
Luo, Jie
;
Ranish, Jeffrey
论文数: 0引用数: 0
h-index: 0
机构:
Inst Syst Biol, Seattle, WA USAFred Hutchinson Canc Res Ctr, Div Basic Sci, Seattle, WA 98104 USA
Ranish, Jeffrey
;
Hahn, Steven
论文数: 0引用数: 0
h-index: 0
机构:
Fred Hutchinson Canc Res Ctr, Div Basic Sci, Seattle, WA 98104 USAFred Hutchinson Canc Res Ctr, Div Basic Sci, Seattle, WA 98104 USA
机构:
Univ Western Ontario, Dept Biochem, Schulich Sch Med & Dent, London, ON N6A 5C1, CanadaUniv Western Ontario, Dept Biochem, Schulich Sch Med & Dent, London, ON N6A 5C1, Canada
Genereaux, Julie
;
Kvas, Stephanie
论文数: 0引用数: 0
h-index: 0
机构:
Univ Western Ontario, Dept Biochem, Schulich Sch Med & Dent, London, ON N6A 5C1, CanadaUniv Western Ontario, Dept Biochem, Schulich Sch Med & Dent, London, ON N6A 5C1, Canada
Kvas, Stephanie
;
Dobransky, Dominik
论文数: 0引用数: 0
h-index: 0
机构:
Univ Western Ontario, Dept Biochem, Schulich Sch Med & Dent, London, ON N6A 5C1, CanadaUniv Western Ontario, Dept Biochem, Schulich Sch Med & Dent, London, ON N6A 5C1, Canada
Dobransky, Dominik
;
Karagiannis, Jim
论文数: 0引用数: 0
h-index: 0
机构:
Univ Western Ontario, Dept Biol, London, ON N6A 5B7, CanadaUniv Western Ontario, Dept Biochem, Schulich Sch Med & Dent, London, ON N6A 5C1, Canada
Karagiannis, Jim
;
Gloor, Gregory B.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Western Ontario, Dept Biochem, Schulich Sch Med & Dent, London, ON N6A 5C1, CanadaUniv Western Ontario, Dept Biochem, Schulich Sch Med & Dent, London, ON N6A 5C1, Canada
Gloor, Gregory B.
;
Brandl, Christopher J.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Western Ontario, Dept Biochem, Schulich Sch Med & Dent, London, ON N6A 5C1, CanadaUniv Western Ontario, Dept Biochem, Schulich Sch Med & Dent, London, ON N6A 5C1, Canada
机构:
Fred Hutchinson Canc Res Ctr, Div Basic Sci, Seattle, WA 98104 USA
Univ Washington, Biol Phys Struct & Design Program, Seattle, WA 98195 USAFred Hutchinson Canc Res Ctr, Div Basic Sci, Seattle, WA 98104 USA
Han, Yan
;
Luo, Jie
论文数: 0引用数: 0
h-index: 0
机构:
Inst Syst Biol, Seattle, WA USAFred Hutchinson Canc Res Ctr, Div Basic Sci, Seattle, WA 98104 USA
Luo, Jie
;
Ranish, Jeffrey
论文数: 0引用数: 0
h-index: 0
机构:
Inst Syst Biol, Seattle, WA USAFred Hutchinson Canc Res Ctr, Div Basic Sci, Seattle, WA 98104 USA
Ranish, Jeffrey
;
Hahn, Steven
论文数: 0引用数: 0
h-index: 0
机构:
Fred Hutchinson Canc Res Ctr, Div Basic Sci, Seattle, WA 98104 USAFred Hutchinson Canc Res Ctr, Div Basic Sci, Seattle, WA 98104 USA