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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2020.1
- 수록면
- 705 - 717 (13page)
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While the growth factors like insulin initiate a signaling cascade to induce conformational changes in the mechanistic target of rapamycin complex 1 (mTORC1), amino acids cause the complex to localize to the site of activation, the lysosome. The precise mechanism of how mTORC1 moves in and out of the lysosome is yet to be elucidated in detail. Here we report that microtubules and the motor protein KIF11 are required for the proper dissociation of mTORC1 from the lysosome upon amino acid scarcity. When microtubules are disrupted or KIF11 is knocked down, we observe that mTORC1 localizes to the lysosome even in the amino acid-starved situation where it should be dispersed in the cytosol, causing an elevated mTORC1 activity. Moreover, in the mechanistic perspective, we discover that mTORC1 interacts with KIF11 on the motor domain of KIF11, enabling the complex to move out of the lysosome along microtubules. Our results suggest not only a novel way of the regulation regarding amino acid availability for mTORC1, but also a new role of KIF11 and microtubules in mTOR signaling.
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참고문헌 (46)
참고문헌 신청
Bar-Peled, L. / 2013 / A Tumor suppressor complex with GAP activity for the Rag GTPases that signal amino acid sufficiency to mTORC1 / Science 340:1100~1106
Burnett, P. E. / 1998 / RAFT1 phosphorylation of the translational regulators p70 S6 kinase and 4E-BP1 / Proc. Natl. Acad. Sci. U. S. A 95:1432~1437
Chantranupong, L. / 2016 / The CASTOR proteins are arginine sensors for the mTORC1 pathway / Cell 165:153~164
Chung, J. / 1992 / Rapamycin-FKBP specifically blocks growth-dependent activation of and signaling by the 70 kd S6 protein kinases / Cell 69:1227~1236
Cole, D. G. / 1994 / A"slow"homotetrameric kinesin-related motor protein purified from Drosophila embryos / J. Biol. Chem 269:22913~22916
Burnett, P. E. / 1998 / RAFT1 phosphorylation of the translational regulators p70 S6 kinase and 4E-BP1 / Proc. Natl. Acad. Sci. U. S. A 95:1432~1437
Chantranupong, L. / 2016 / The CASTOR proteins are arginine sensors for the mTORC1 pathway / Cell 165:153~164
Chung, J. / 1992 / Rapamycin-FKBP specifically blocks growth-dependent activation of and signaling by the 70 kd S6 protein kinases / Cell 69:1227~1236
Cole, D. G. / 1994 / A"slow"homotetrameric kinesin-related motor protein purified from Drosophila embryos / J. Biol. Chem 269:22913~22916
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