Biological Activity
remodelin is a potent inhibitor of nat10 [1].n-acetyltransferase 10 (nat10) is the only identified lysine acetyltransferase that acts on microtubules and histones [1]. nat10 mainly exists in the nucleolus.remodelin is a potent nat10 inhibitor. in lamin a/c depletion (silmna) cells, remodelin remodeled nuclear architecture through inhibition of nat10 lysine acetyltransferase activity. in cells derived from lmna-mutated hgps patients and primary mrc5 fibroblasts aged in culture, remodelin significantly decreased the prevalence of misshapen nuclei. in u2os cells and normal fibroblasts, remodelin inhibited nuclear shape defects induced by farnesyltransferase inhibitors (fti). in hgps cells, remodelin reduced the amount of misshapen nuclei, suggesting that inhibition of nat10 mediated nuclear shape normalization. also, remodelin reduced dna damage signaling, reduced sun1 accumulation at the nuclear envelope, reduced the levels of autophosphorylated atm and dna double-strand break markers γh2ax, and improved chromatin and nucleolar organization. in silmna and hgps cells, remodelin inhibited microtubule anchorage to centrosomes [1].
References
[1]. larrieu d, britton s, demir m, et al. chemical inhibition of nat10 corrects defects of laminopathic cells. science, 2014, 344(6183): 527-532.
