title: Identification and characterization of molecular interactions between mortalin/mtHsp70 and HSP60.
abstract: Mortalin/mtHsp70 (mitochondrial Hsp70) and HSP60 (heat-shock protein 60) are heat-shock proteins that reside in multiple subcellular compartments, with mitochondria being the predominant one. In the present study, we demonstrate that the two proteins interact both in vivo and in vitro, and that the N-terminal region of mortalin is involved in these interactions. Suppression of HSP60 expression by shRNA (short hairpin RNA) plasmids caused the growth arrest of cancer cells similar to that obtained by suppression of mortalin expression by ribozymes. An overexpression of mortalin, but not of HSP60, extended the in vitro lifespan of normal fibroblasts (TIG-1). Taken together, this study for the first time delineates: (i) molecular interactions of HSP60 with mortalin; (ii) their co- and exclusive localizations in vivo; (iii) their involvement in tumorigenesis; and (iv) their functional distinction in pathways involved in senescence.
authors.affiliation: Gene Function Research Center, National Institute of Advanced Industrial Science & Technology (AIST), 1-1-1 Higashi, Tsukuba, Ibaraki 305-8562, Japan.
authors.forename: Renu
authors.initials: R
authors.lastname: Wadhwa
authors.forename: Syuichi
authors.initials: S
authors.lastname: Takano
authors.forename: Kamaljit
authors.initials: K
authors.lastname: Kaur
authors.forename: Satoshi
authors.initials: S
authors.lastname: Aida
authors.forename: Tomoko
authors.initials: T
authors.lastname: Yaguchi
authors.forename: Zeenia
authors.initials: Z
authors.lastname: Kaul
authors.forename: Takashi
authors.initials: T
authors.lastname: Hirano
authors.forename: Kazunari
authors.initials: K
authors.lastname: Taira
authors.forename: Sunil C
authors.initials: SC
authors.lastname: Kaul
mesh_terms: D002455:Cell Division; D002460:Cell Line; D016922:Cellular Senescence; D018834:Chaperonin 60 / Q000235:genetics / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D017353:Gene Deletion; D005786:Gene Expression Regulation; D018840:HSP70 Heat-Shock Proteins / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D024101:Mitochondrial Proteins / Q000378:metabolism*; D012516:Osteosarcoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011485:Protein Binding; D034622:RNA Interference
chemical_list: D018834:Chaperonin 60; D018840:HSP70 Heat-Shock Proteins; D024101:Mitochondrial Proteins; C080352:mortalin