標題: AMP-Activated Protein Kinase Directly Phosphorylates and Destabilizes Hedgehog Pathway Transcription Factor GLI1 in Medulloblastoma
作者: Li, Yen-Hsing
Luo, Jia
Mosley, Yung-Yi C.
Hedrick, Victoria E.
Paul, Lake N.
Chang, Julia
Zhang, GuangJun
Wang, Yu-Kuo
Banko, Max R.
Brunet, Anne
Kuang, Shihuan
Wu, Jen-Leih
Chang, Chun-Ju
Scott, Matthew P.
Yang, Jer-Yen
生物科技學系
Department of Biological Science and Technology
公開日期: 28-Jul-2015
摘要: The Hedgehog (Hh) pathway regulates cell differentiation and proliferation during development by controlling the Gli transcription factors. Cell fate decisions and progression toward organ and tissue maturity must be coordinated, and how an energy sensor regulates the Hh pathway is not clear. AMP-activated protein kinase (AMPK) is an important sensor of energy stores and controls protein synthesis and other energy-intensive processes. AMPK is directly responsive to intracellular AMP levels, inhibiting a wide range of cell activities if ATP is low and AMP is high. Thus, AMPK can affect development by influencing protein synthesis and other processes needed for growth and differentiation. Activation of AMPK reduces GLI1 protein levels and stability, thus blocking Sonic-hedgehog-induced transcriptional activity. AMPK phosphorylates GLI1 at serines 102 and 408 and threonine 1074. Mutation of these three sites into alanine prevents phosphorylation by AMPK. This leads to increased GLI1 protein stability, transcriptional activity, and oncogenic potency.
URI: http://dx.doi.org/10.1016/j.celrep.2015.06.054
http://hdl.handle.net/11536/128024
ISSN: 2211-1247
DOI: 10.1016/j.celrep.2015.06.054
期刊: CELL REPORTS
Volume: 12
Issue: 4
起始頁: 599
結束頁: 609
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