激酶Aurora-A调控细胞分裂期中心体的成熟、分离和纺锤体的正确形成。Aurora-A在很多肿瘤亚型中扩增或过表达，是肿瘤恶性程度高和预后差的标志分子。但是目前对Aurora-A调控细胞增殖以及肿瘤发展过程的分子机理还不清楚。我们在前期研究中发现并验证了Aurora-A可以与代谢酶LDHB相互作用。LDHB是组成乳酸脱氢酶的两个亚基之一，催化糖酵解生成的丙酮酸与乳酸的相互转化，是糖代谢的关键酶。进一步的研究发现Aurora-A可以通过直接磷酸化LDHB调控其酶活性以及催化反应的方向。突变Aurora-A磷酸化LDHB的位点抑制肿瘤细胞的增殖。在本申请课题中，我们计划进一步鉴定这两个蛋白相互作用的时空关系，以及在细胞周期和能量物质代谢中的功能。我们还将研究Aurora-A与LDHB的相互调节在细胞增殖以及肿瘤恶性发展过程的作用，揭示细胞周期与细胞代谢协同调控细胞增殖的新机制。

Aurora-A kinase functions in centrosome maturation, separation and bi-polar spindle formation during cell division cycle. Amplification and overexpression of Aurora-A have been reported in a number of human tumors and have been identified as a biomarker for tumor malignant progression and poor prognosis. However, how Aurora-A is involved in the regulation of cancer cell proliferation and tumor progression remain elusive. In this project, we found and further validated that Aurora-A is associated with lactate dehydrogenase B, the subunit of tetrameric enzyme catalyzing the inter-change between pyruvate and lactate. Kinase assay and Mass spectrum data indicate that Aurora-A phosphorylates LDHB directly. We further demonstrated that this modification changes the rate and direction of the enzyme, which is required for the tumor cell proliferation. Next, we propose to further examine the temp-spatial regulation and the function of Aurora-A-LDHB interaction in the regulation of cell cycle and cell metabolism, two fundamental activities of a cell. The physiological and pathological relevance of this pathway will be also evaluated. We expect to reveal a new mechanism that coordinates cell cycle and metabolism to promote proliferation.