BACKGROUND: SIRT1 is a mammalian homologue of NAD+-dependent deacetylase sirtuin 
family. It regulates longevity in several model organisms and is involved with 
cell survival, differentiation, metabolism among other processes in mammalian 
cells. SIRT1 modulates functions of various key targets via deacetylation. 
Recent studies have revealed SIRT1 protects neurons from axonal degeneration or 
neurodegeneration. Further, SIRT1 null mice exhibit growth retardation and 
developmental defects, suggesting its critical roles in neurons and development.
RESULTS: To identify novel binding partners for SIRT1 in the central nervous 
system, we performed yeast two-hybrid screening on human fetal brain cDNA 
library and found that zyxin is a possible binding partner. SIRT1 and zyxin 
transcript were both preferentially expressed in developmental mouse brain. 
Zyxin accumulates in the nucleus where it is co-localized with SIRT1 after 
treatment with leptomycin B in COS-7 cells. Furthermore, SIRT1 deacetylates 
zyxin, suggesting SIRT1 could interact with nuclear-accumulated zyxin and 
modulate its function through deacetylation.
CONCLUSION: Zyxin could be a novel interacting partner of SIRT1. Zyxin is an 
adaptor protein at focal adhesion plaque, regulating cytoskeletal dynamics and 
signal transduction to convey signal from the ECM (extracellular matrix) to the 
nucleus. Our results raise the possibility that SIRT1 regulates signal 
transmission from ECM to the nucleus by modulating the functions of zyxin via 
deacetylation.