A NOVEL F BOX PROTEIN REGULATING MITOSIS

描述（来自申请人摘要的逐字记录）： 细胞周期蛋白B和细胞周期蛋白B/Cdc 2激酶的激活驱动有丝分裂。的 细胞周期蛋白B被有丝分裂激活的泛素连接酶泛素化， 后期促进复合物（APC），以及随后的细胞周期蛋白B的破坏 是有丝分裂退出的关键一类独特的泛素连接酶，称为 SCF复合物，控制着许多细胞周期的转换，包括G1-S G2-M转换SCF复合物包含含有F盒基序的蛋白质。 这些F盒蛋白是允许SCF复合物结合的衔接蛋白 到遍在化目标。调查人员发现了一个新的F盒， SBP 5，控制有丝分裂的进入和退出。很像有丝分裂 细胞周期蛋白，SBP 5是有丝分裂进入所必需的，并且必须被破坏以进行有丝分裂。 退出. SBP 5阻断有丝分裂出口的能力是由于它的靶向作用， APC的调节亚基，称为Cdc 2 O。SPB 5在有丝分裂中被破坏，但 一个独立于APC的机制。SPB 5也定位于有丝分裂纺锤体。 他们怀疑与SBP 5相关的泛素连接酶活性介导了 有丝分裂纺锤体调节器的破坏。SBP 5的过表达 诱导中期停滞、纺锤体异常和凋亡。目标 包括（1）SBP 5的生化和突变研究;（2）确定 SBP 5与有丝分裂纺锤体的相互作用;（3）体外研究， SBP 5相关的泛素连接酶活性;和（4）人同源物的研究 关于SBP 5通过将纺锤体控制与中期阻滞和细胞凋亡相结合， 可能参与微管毒素如紫杉醇和长春花的途径 生物碱用来触发细胞死亡。了解SBP 5如何阻止有丝分裂， 诱导细胞凋亡可能为创造新的癌症提供重要的见解 与长春花碱作用类似或协同的化疗药物 生物碱和紫杉醇。

DESCRIPTION (Verbatim from the applicant's abstract): The accumulation of cyclin B and activation of the cyclin B/Cdc2 kinase drives mitosis. The ubiquitination of cyclin B by a mitotically activated ubiquitin ligase, the Anaphase Promoting Complex (APC), and the subsequent destruction of cyclin B are critical for mitotic exit. A distinct class of ubiquitin ligases, called SCF complexes, control a number of cell cycle transitions, including the G 1-S and G2-M transitions. SCF complexes contain proteins that contain F-box motifs. These F-box proteins are adapter proteins that allow the SCF complexes to bind to ubiquitination targets. The investigator has discovered a new F-box called SBP5 that controls the entry into and exit from mitosis. Much like the mitotic cyclins, SBP5 is required for mitotic entry and must be destroyed for mitotic exit. The ability for SBP5 to block mitotic exit results from its targeting a regulatory subunit of the APC, called Cdc2O. SPB5 is destroyed in mitosis, but by an APC-independent mechanism. SPB5 also localizes to the mitotic spindle. They suspect that an SBP5-associated ubiquitin ligase activity mediates destruction of regulators of the mitotic spindle. Overexpression of SBP5 induces a metaphase arrest, spindle abnormalities, and apoptosis. The aims include (1) Biochemical and mutational studies of SBP5; (2) defining the interaction of SBP5 with the mitotic spindle; (3) in vitro studies of an SBP5-associated ubiquitin ligase activity; and (4) studies of a human homolog of SBP5. By coupling spindle control to a metaphase block and apoptosis, SBP5 may participate in the pathway that microtubule poisons like Taxol and vinca alkaloids use to trigger cell death. Understanding how SBP5 blocks mitosis and induces apoptosis may provide important insight for creating new cancer chemotherapeutic drugs that act similarly or synergistically with vinca alkaloids and Taxol.