Department of Biological Sciences, Stanford University, CA 94305-5020, USA.
Biochem Biophys Res Commun. 2010 Mar 5;393(2):259-63. doi: 10.1016/j.bbrc.2010.01.115. Epub 2010 Feb 1.
DDA3 is a microtubule-associated protein that controls chromosome congression and segregation by regulating the mitotic spindle. Depletion of DDA3 alters spindle structure, generates unaligned chromosomes at metaphase, and delays the mitotic progression. Through a mass spectrometry analysis, we found that DDA3 is phosphorylated on Ser225 during mitosis. Phosphorylation of this residue is important for the mitotic function of DDA3, as the phospho-mimicking DDA3-S225D variant, but not the nonphosphorable DDA3-S225A mutant, rescues the DDA3-knockdown phenotype. We conclude that the mitotic function of DDA3 is regulated by phosphorylation on the Ser225 residue.
DDA3 是一种微管相关蛋白，通过调节有丝分裂纺锤体控制染色体的向心运动和分离。DDA3 的耗竭会改变纺锤体结构，在中期产生未对齐的染色体，并延迟有丝分裂进程。通过质谱分析，我们发现 DDA3 在有丝分裂过程中丝氨酸 225 位发生磷酸化。该残基的磷酸化对于 DDA3 的有丝分裂功能很重要，因为磷酸化模拟的 DDA3-S225D 变体，但不是不可磷酸化的 DDA3-S225A 突变体，可以挽救 DDA3 敲低表型。我们得出结论，DDA3 的有丝分裂功能受丝氨酸 225 残基磷酸化的调节。
