Division of Oncology-Hematology, Department of Medicine, Sylvester Comprehensive Cancer Center, University of Miami, FL 33136, USA.
FEBS J. 2011 Jun;278(11):1922-31. doi: 10.1111/j.1742-4658.2011.08109.x. Epub 2011 Apr 20.
Human germinal center associated lymphoma (HGAL) is a germinal center-specific gene whose expression correlates with a favorable prognosis in patients with diffuse large B-cell and classic Hodgkin lymphomas. HGAL is involved in negative regulation of lymphocyte motility. The movement of lymphocytes is directly driven by actin polymerization and actin-myosin interactions. We demonstrate that HGAL interacts directly and independently with both actin and myosin and delineate the HGAL and myosin domains responsible for the interaction. Furthermore, we show that HGAL increases the binding of myosin to F-actin and inhibits the ability of myosin to translocate actin by reducing the maximal velocity of myosin head/actin movement. No effects of HGAL on actomyosin ATPase activity and the rate of actin polymerization from G-actin to F-actin were observed. These findings reveal a new mechanism underlying the inhibitory effects of germinal center-specific HGAL protein on lymphocyte and lymphoma cell motility.
人类生发中心相关淋巴瘤(HGAL)是一种生发中心特异性基因,其表达与弥漫性大 B 细胞淋巴瘤和经典霍奇金淋巴瘤患者的良好预后相关。HGAL 参与淋巴细胞迁移的负调控。淋巴细胞的运动直接由肌动蛋白聚合和肌球蛋白-肌动蛋白相互作用驱动。我们证明 HGAL 直接且独立地与肌动蛋白和肌球蛋白相互作用,并描绘了负责相互作用的 HGAL 和肌球蛋白结构域。此外,我们表明 HGAL 增加了肌球蛋白与 F-肌动蛋白的结合,并通过降低肌球蛋白头部/肌动蛋白运动的最大速度来抑制肌球蛋白转运肌动蛋白的能力。未观察到 HGAL 对肌球蛋白-肌动球蛋白 ATP 酶活性和从 G-肌动蛋白到 F-肌动蛋白的肌动蛋白聚合速率的影响。这些发现揭示了生发中心特异性 HGAL 蛋白对淋巴细胞和淋巴瘤细胞迁移的抑制作用的新机制。