title: Deacetylated αβ-tubulin acts as a positive regulator of Rheb GTPase through increasing its GTP-loading.
abstract: Ras homolog enriched in brain (Rheb) regulates diverse cellular functions by modulating its nucleotide-bound status. Although Rheb contains a high basal GTP level, the regulatory mechanism of Rheb is not well understood. In this study, we propose soluble αβ-tubulin acts as a constitutively active Rheb activator, which may explain the reason why Rheb has a high basal GTP levels. We found that soluble αβ-tubulin is a direct Rheb-binding protein and that its deacetylated form has a high binding affinity for Rheb. Modulation of both soluble and acetylated αβ-tubulin levels affects the level of GTP-bound Rheb. This occurs in the mitotic phase in which the level of acetylated αβ-tubulin is increased but that of GTP-bound Rheb is decreased. Constitutively active Rheb-overexpressing cells showed an abnormal mitotic progression, suggesting the deacetylated αβ-tubulin-mediated regulation of Rheb status may be important for proper mitotic progression. Taken together, we propose that deacetylated soluble αβ-tubulin is a novel type of positive regulator of Rheb and may play a role as a temporal regulator for Rheb during the cell cycle.
authors.affiliation: Division of Molecular and Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang 790-784, Republic of Korea.
authors.forename: Mi Nam
authors.initials: MN
authors.lastname: Lee
authors.forename: Ara
authors.initials: A
authors.lastname: Koh
authors.forename: Dohyun
authors.initials: D
authors.lastname: Park
authors.forename: Jin-Hyeok
authors.initials: JH
authors.lastname: Jang
authors.forename: Dongoh
authors.initials: D
authors.lastname: Kwak
authors.forename: Hyeona
authors.initials: H
authors.lastname: Jeon
authors.forename: Jaeyoon
authors.initials: J
authors.lastname: Kim
authors.forename: Eun-Jeong
authors.initials: EJ
authors.lastname: Choi
authors.forename: Heeyoon
authors.initials: H
authors.lastname: Jeong
authors.forename: Pann-Ghill
authors.initials: PG
authors.lastname: Suh
authors.forename: Sung Ho
authors.initials: SH
authors.lastname: Ryu
mesh_terms: D000107:Acetylation; D045744:Cell Line, Tumor; D006160:Guanosine Triphosphate / Q000378:metabolism*; D057809:HEK293 Cells; D006367:HeLa Cells; D006639:Histidine / Q000235:genetics / Q000378:metabolism; D006801:Humans; D061986:MCF-7 Cells; D008870:Microtubules / Q000378:metabolism; D008938:Mitosis; D020559:Monomeric GTP-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009479:Neuropeptides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009842:Oligopeptides / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D000076205:Ras Homolog Enriched in Brain Protein; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics; D014162:Transfection; D014404:Tubulin / Q000378:metabolism*
chemical_list: C471213:His-His-His-His-His-His; D009479:Neuropeptides; D009842:Oligopeptides; C490211:RHEB protein, human; D000076205:Ras Homolog Enriched in Brain Protein; D011993:Recombinant Fusion Proteins; D014404:Tubulin; D006639:Histidine; D006160:Guanosine Triphosphate; D020559:Monomeric GTP-Binding Proteins