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. Author manuscript; available in PMC: 2012 Jan 9.
Published in final edited form as: Rom J Morphol Embryol. 2011;52(4):1173–1185.

Figure 1.

Figure 1

Cell signaling pathways of SIRT1. The RNA binding protein HuR and a nuclear protein active regulator of SIRT1 (AROS) can promote SIRT1 activity. AMP activated protein kinase (AMPK) can activate SIRT1 through increasing the level of NAD+/NADH ratio, but there exists a positive feedback, activated SIRT1 deacetylates the serine-threonine liver kinase B1 (LKB1) and subsequently activates AMPK. In contrast, hypermethylated in cancer 1 (HIC1) and deleted in breast cancer 1 (DBC1) negatively regulates the activity of SIRT1. Downstream of SIRT1 are the FoxO transcription factors, peroxisome proliferators-activated receptor-γ coactivator-1α (PGC-1α), protein tyrosine phosphatase 1B (PTP1B), p53, nuclear factor-κB (NF-κB), apoptotic transcription regulator E2F1, and the uncoupling protein gene UCP2. SIRT1 can, through modulating its multiple targets, regulate lipid metabolism, insulin secretion and sensitivity, mitochondrial function, and cell survival.