Deacetylated alpha beta-tubulin acts as a positive regulator of Rheb GTPase through increasing its GTP-loading
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- Deacetylated alpha beta-tubulin acts as a positive regulator of Rheb GTPase through increasing its GTP-loading
- Lee, Mi Nam; Koh, Ara; Park, Dohyun; Jang, Jin-Hyeok; Kwak, Dongoh; Jeon, Hyeona; Kim, Jaeyoon; Choi, Eun-Jeong; Jeong, Heeyoon; Suh, Pann-Ghill; Ryu, Sung Ho
- Mitosis; MTOR; Rheb; Soluble tubulin
- Issue Date
- ELSEVIER SCIENCE INC
- CELLULAR SIGNALLING, v.25, no.2, pp.539 - 551
- 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 alpha beta-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 alpha beta-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 alpha beta-tubulin levels affects the level of GTP-bound Rheb. This occurs in the mitotic phase in which the level of acetylated alpha beta-tubulin is increased but that of GTP-bound Rheb is decreased. Constitutively active Rheb-overexpressing cells showed an abnormal mitotic progression, suggesting the deacetylated alpha beta-tubulin-mediated regulation of Rheb status may be important for proper mitotic progression. Taken together, we propose that deacetylated soluble alpha beta-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.
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