Elongator's toxin-target (TOT) function is nuclear localization sequence dependent and suppressed by post-translational modification.
The toxin target (TOT) function of the Saccharomyces cerevisiae Elongator complex enables Kluyveromyces lactis zymocin to induce a G1 cell cycle arrest. Loss of a ubiquitin-related system (URM1-UBA4 ) and KTI11 enhances post-translational modification/proteolysis of Elongator subunit Tot1p (Elp1p) and abrogates its TOT function. Using TAP tagging, Kti11p contacts Elongator and translational proteins (Rps7Ap, Rps19Ap Eft2p, Yil103wp, Dph2p). Loss of YIL103w and DPH2 (involved in diphtheria toxicity) suppresses zymocicity implying that both toxins overlap in a manner mediated by Kti11p. Among the pool that co-fractionates with RNA polymerase II (pol II) and nucleolin, Nop1p, unmodified Tot1p dominates. Thus, modification/proteolysis may affect association of Elongator with pol II or its localization. Consistently, an Elongator-nuclear localization sequence (NLS) targets green fluorescent protein (GFP) to the nucleus, and its truncation yields TOT deficiency. Similarly, KAP120 deletion rescues cells from zymocin, suggesting that Elongator's TOT function requires NLS- and karyopherin-dependent nuclear import.
Fichtner
Lars
L
Biologicum, Institut für Genetik, Martin-Luther-Universität Halle-Wittenberg, Weinbergweg 10, D-06120 Halle (Saale), Germany.
Jablonowski
Daniel
D
Schierhorn
Angelika
A
Kitamoto
Hiroko K
HK
Stark
Michael J R
MJ
Schaffrath
Raffael
R
D021581:Active Transport, Cell Nucleus; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D016193:G1 Phase; D017353:Gene Deletion; D005800:Genes, Fungal; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins; D051548:Histone Acetyltransferases; D028884:Karyopherins / Q000378:metabolism; D055646:Killer Factors, Yeast; D007716:Kluyveromyces / Q000378:metabolism; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D009183:Mycotoxins / Q000378:metabolism*; D019913:Nuclear Localization Signals / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism; D010445:Peptide Elongation Factors / Q000378:metabolism; D025941:Protein Interaction Mapping; D011499:Protein Processing, Post-Translational; D012319:RNA Polymerase II / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D020718:Ribonucleoproteins, Small Nucleolar / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism
D005656:Fungal Proteins; C479560:KAP120 protein, S cerevisiae; C459979:KTI11 protein, S cerevisiae; D028884:Karyopherins; D055646:Killer Factors, Yeast; D008164:Luminescent Proteins; D009183:Mycotoxins; C064793:NOP1 protein, S cerevisiae; D019913:Nuclear Localization Signals; D009687:Nuclear Proteins; D010445:Peptide Elongation Factors; D012097:Repressor Proteins; D020718:Ribonucleoproteins, Small Nucleolar; D029701:Saccharomyces cerevisiae Proteins; C406283:UBA4 protein, S cerevisiae; C406282:URM1 protein, S cerevisiae; C058975:zymocin; D049452:Green Fluorescent Proteins; D051548:Histone Acetyltransferases; C479559:IKI3 protein, S cerevisiae; D012319:RNA Polymerase II