Akt acutely activates the cholesterogenic transcription factor SREBP-2

作者：Luu Winnie; Sharpe Laura J; Stevenson Julian; Brown Andrew J^*

来源：Biochimica et Biophysica Acta-Molecular Cell Research, 2012, 1823(2): 458-464.

DOI：10.1016/j.bbamcr.2011.09.017

• Akt
• Cholesterol
• IGF-1
• PI3K
• SREBP-2

Akt is an essential protein kinase for cell growth, proliferation, and survival. Perturbed Akt regulation is associated with a number of human diseases, such as cancer and diabetes. Recently, evidence has emerged that Akt is involved in the regulation of the sterol-regulatory element binding proteins, which are master transcriptional regulators of lipid metabolism. This offers a means by which synthesis of new membrane can be coordinated with cell growth and proliferation. However, the link between Akt and sterol-regulatory element binding protein-2, the major isoform participating in cholesterol regulation, is relatively unexplored. In the present study, we employed insulin-like growth factor-1 as an inducer of Akt signalling, and showed that it increased sterol-regulatory element binding protein-2 activation acutely (within 1 h). This insulin-like growth factor-1-induced sterol-regulatory element binding protein-2 activation was blunted when Akt was inhibited pharmacologically or molecularly with small interfering RNA. Furthermore, we employed a rapalog heterodimerisation system to specifically and rapidly activate Akt, and found that sterol-regulatory element binding protein-2 activation was increased in response to Akt activation. Together, this study provides compelling evidence that Akt contributes to the acute regulation of cholesterol metabolism through activating sterol-regulatory element binding protein-2.