title: CK2 phospho-independent assembly of the Tel2-associated stress-signaling complexes in Schizosaccharomyces pombe.
abstract: An evolutionarily conserved protein Tel2 regulates a variety of stress signals. In mammals, TEL2 associates with TTI1 and TTI2 to form the Triple T (TTT: TEL2-TTI1-TTI2) complex as well as with all the phosphatidylinositol 3-kinase-like kinases (PIKKs) and the R2TP (Ruvbl1-Ruvbl2-Tah1-Pih1 in budding yeast)/prefoldin-like complex that associates with HSP90. The phosphorylation of TEL2 by casein kinase 2 (CK2) enables direct binding of PIHD1 (mammalian Pih1) to TEL2 and is important for the stability and the functions of PIKKs. However, the regulatory mechanisms of Tel2 in fission yeast Schizosaccharomyces pombe remain largely unknown. Here, we report that S. pombe Tel2 is phosphorylated by CK2 at Ser490 and Thr493. Tel2 forms the TTT complex with Tti1 and Tti2 and also associates with PIKKs, Rvb2, and Hsp90 in vivo; however, the phosphorylation of Tel2 affects neither the stability of the Tel2-associated proteins nor their association with Tel2. Thus, Tel2 stably associates with its binding partners irrespective of its phosphorylation. Furthermore, the Tel2 phosphorylation by CK2 is not required for the various stress responses to which PIKKs are pivotal. Our results suggest that the Tel2-containing protein complexes are conserved among eukaryotes, but the molecular regulation of their formation has been altered during evolution.
authors.affiliation: Institute for Protein Research, Osaka University, 3-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
authors.forename: Haruna
authors.initials: H
authors.lastname: Inoue
authors.affiliation: Institute for Protein Research, Osaka University, 3-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
authors.forename: Shizuka
authors.initials: S
authors.lastname: Sugimoto
authors.affiliation: Institute for Protein Research, Osaka University, 3-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Takeshita
authors.affiliation: Institute for Protein Research, Osaka University, 3-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
authors.forename: Miho
authors.initials: M
authors.lastname: Takeuchi
authors.affiliation: Okinawa Institute of Science and Technology Graduate University, 1919-1 Tancha, Onna, Okinawa, 909-0495, Japan.
authors.forename: Mitsuko
authors.initials: M
authors.lastname: Hatanaka
authors.affiliation: Okinawa Institute of Science and Technology Graduate University, 1919-1 Tancha, Onna, Okinawa, 909-0495, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Nagao
authors.affiliation: Okinawa Institute of Science and Technology Graduate University, 1919-1 Tancha, Onna, Okinawa, 909-0495, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Hayashi
authors.affiliation: Okinawa Institute of Science and Technology Graduate University, 1919-1 Tancha, Onna, Okinawa, 909-0495, Japan.
authors.forename: Aya
authors.initials: A
authors.lastname: Kokubu
authors.affiliation: Okinawa Institute of Science and Technology Graduate University, 1919-1 Tancha, Onna, Okinawa, 909-0495, Japan.
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Yanagida
authors.affiliation: Institute for Protein Research, Osaka University, 3-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
authors.forename: Junko
authors.initials: J
authors.lastname: Kanoh
mesh_terms: D047390:Casein Kinase II / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D012568:Schizosaccharomyces / Q000235:genetics / Q000378:metabolism; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000378:metabolism*; D013312:Stress, Physiological / Q000235:genetics*; D034501:Telomere-Binding Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D046912:Multiprotein Complexes; D029702:Schizosaccharomyces pombe Proteins; C518817:Tel2 protein, S pombe; D034501:Telomere-Binding Proteins; D047390:Casein Kinase II