Chih-Wen Chu

Publications (2)16.24 Total impact

• Article: A novel acetylation of β-tubulin by San modulates microtubule polymerization via down-regulating tubulin incorporation.

  Chih-Wen Chu, Fajian Hou, Junmei Zhang, Lilian Phu, Alex V Loktev, Donald S Kirkpatrick, Peter K Jackson, Yingming Zhao, Hui Zou
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  ABSTRACT: Dynamic instability is a critical property of microtubules (MTs). By regulating the rate of tubulin polymerization and depolymerization, cells organize the MT cytoskeleton to accommodate their specific functions. Among many processes, posttranslational modifications of tubulin are implicated in regulating MT functions. Here we report a novel tubulin acetylation catalyzed by acetyltransferase San at lysine 252 (K252) of β-tubulin. This acetylation, which is also detected in vivo, is added to soluble tubulin heterodimers but not tubulins in MTs. The acetylation-mimicking K252A/Q mutants were incorporated into the MT cytoskeleton in HeLa cells without causing any obvious MT defect. However, after cold-induced catastrophe, MT regrowth is accelerated in San-siRNA cells while the incorporation of acetylation-mimicking mutant tubulins is severely impeded. K252 of β-tubulin localizes at the interface of α-/β-tubulins and interacts with the phosphate group of the α-tubulin-bound GTP. We propose that the acetylation slows down tubulin incorporation into MTs by neutralizing the positive charge on K252 and allowing tubulin heterodimers to adopt a conformation that disfavors tubulin incorporation.
  Molecular biology of the cell 02/2011; 22(4):448-56. · 5.98 Impact Factor
• Source

  Available from: PubMed Central

  Article: The acetyltransferase activity of San stabilizes the mitotic cohesin at the centromeres in a shugoshin-independent manner.

  Fajian Hou, Chih-Wen Chu, Xiangduo Kong, Kyoko Yokomori, Hui Zou
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  ABSTRACT: Proper sister chromatid cohesion is critical for maintaining genetic stability. San is a putative acetyltransferase that is important for sister chromatid cohesion in Drosophila melanogaster, but not in budding yeast. We showed that San is critical for sister chromatid cohesion in HeLa cells, suggesting that this mechanism may be conserved in metazoans. Furthermore, although a small fraction of San interacts with the NatA complex, San appears to mediate cohesion independently. San exhibits acetyltransferase activity in vitro, and its activity is required for sister chromatid cohesion in vivo. In the absence of San, Sgo1 localizes correctly throughout the cell cycle. However, cohesin is no longer detected at the mitotic centromeres. Furthermore, San localizes to the cytoplasm in interphase cells; thus, it may not gain access to chromosomes until mitosis. Moreover, in San-depleted cells, further depletion of Plk1 rescues the cohesion along the chromosome arms, but not at the centromeres. Collectively, San may be specifically required for the maintenance of the centromeric cohesion in mitosis.
  The Journal of Cell Biology 06/2007; 177(4):587-97. · 10.26 Impact Factor