The Multifunctional Protein BAG3: A Novel Therapeutic Target in Cardiovascular Disease.
The Multifunctional Protein BAG3: A Novel Therapeutic Target in Cardiovascular Disease.
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DOI：
10.1016/j.jacbts.2017.09.009
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发表时间：
2018-03
期刊：
影响因子：
--
通讯作者：
Feldman AM
中科院分区：
文献类型：
--
作者：
Myers VD;McClung JM;Wang J;Tahrir FG;Gupta MK;Gordon J;Kontos CH;Khalili K;Cheung JY;Feldman AM
B细胞淋巴瘤2相关的蒽原（BAG 3）蛋白在心脏、骨骼肌和许多形式的癌症中表达最显著。在心脏中，它与热休克蛋白一起作为辅助分子伴侣促进自噬;与B细胞淋巴瘤2结合，导致细胞凋亡抑制;将肌动蛋白附着于Z盘，为肌节提供结构支持;并将α-肾上腺素能受体与L型Ca 2+通道连接。当BAG 3在癌细胞中过表达时，它促进促生存途径，导致对化疗不敏感，转移，细胞迁移和侵袭。相比之下，在心脏中，BAG 3的突变与各种表型相关，包括肥厚性/限制性和扩张性心肌病。在小鼠骨骼肌和血管系统中，BAG 3突变导致股动脉结扎后严重肢体缺血。对BAG 3生物学的理解是相关的，因为它可以为心脏和骨骼肌疾病患者提供治疗靶点。
The B-cell lymphoma 2–associated anthanogene (BAG3) protein is expressed most prominently in the heart, the skeletal muscle, and in many forms of cancer. In the heart, it serves as a co-chaperone with heat shock proteins in facilitating autophagy; binds to B-cell lymphoma 2, resulting in inhibition of apoptosis; attaches actin to the Z disk, providing structural support for the sarcomere; and links the α-adrenergic receptor with the L-type Ca2+ channel. When BAG3 is overexpressed in cancer cells, it facilitates prosurvival pathways that lead to insensitivity to chemotherapy, metastasis, cell migration, and invasiveness. In contrast, in the heart, mutations in BAG3 have been associated with a variety of phenotypes, including both hypertrophic/restrictive and dilated cardiomyopathy. In murine skeletal muscle and vasculature, a mutation in BAG3 leads to critical limb ischemia after femoral artery ligation. An understanding of the biology of BAG3 is relevant because it may provide a therapeutic target in patients with both cardiac and skeletal muscle disease.
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