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微管破坏药物引发bcl2磷酸化——bcl2蛋白丝氨酸-70和丝氨酸-87残基上均需要磷酸化。

Microtubule-damaging drugs triggered bcl2 phosphorylation-requirement of phosphorylation on both serine-70 and serine-87 residues of bcl2 protein.

作者信息

Basu A, Haldar S

机构信息

Rammelkamp Center for Education and Research, Department of Pharmacology, Ireland Cancer Center, MetroHealth/Case Western Reserve University, Cleveland, OH 44109-1998, USA.

出版信息

Int J Oncol. 1998 Oct;13(4):659-64. doi: 10.3892/ijo.13.4.659.

Abstract

Specifically anti-microtubule agents such as taxol, vincristine, vinblastine and dolastatin can trigger Bcl2 phosphorylation at G2-M phase of the cell cycle in malignant cells derived from a variety of human cancers. In this study, the status of Bcl2 phosphorylation was investigated in response to more antimicrotubule agents such as colchicine, colcemid or podophyllotoxin. Although these agents are not currently used for cancer therapy, they were able to trigger Bcl2 phosphorylation with simultaneous apoptosis in cancer cells. Previously, by using extensive site-directed mutagenesis studies we determined that mutation of serine-70 to alanine could not completely abrogate taxol induced Bcl2 phosphorylation. Studies reported here clearly indicate that serine-87 residue along with serine-70 of Bcl2 protein are necessary for microtubule damaging drug induced phosphorylation.

摘要

具体而言,诸如紫杉醇、长春新碱、长春花碱和多拉司他汀等抗微管药物可在源自多种人类癌症的恶性细胞的细胞周期G2-M期触发Bcl2磷酸化。在本研究中,针对更多抗微管药物如秋水仙碱、秋水仙酰胺或鬼臼毒素,研究了Bcl2磷酸化的状态。尽管这些药物目前未用于癌症治疗,但它们能够在癌细胞中触发Bcl2磷酸化并同时诱导凋亡。此前,通过广泛的定点诱变研究,我们确定将丝氨酸-70突变为丙氨酸并不能完全消除紫杉醇诱导的Bcl2磷酸化。此处报道的研究清楚地表明,Bcl2蛋白的丝氨酸-87残基以及丝氨酸-70对于微管损伤药物诱导的磷酸化是必需的。

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