Gelman Irwin H
Department of Cancer Genetics, Roswell Park Cancer Institute, Buffalo, NY, USA.
Genes Cancer. 2010 Nov;1(11):1147-56. doi: 10.1177/1947601910392984.
Emerging data suggest that SSeCKS/Gravin/AKAP12 ("AKAP12"), originally identified as an autoantigen in cases of myasthenia gravis, controls multiple biological processes through its ability to scaffold key signaling proteins such as protein kinase (PK) C and A, calmodulin, cyclins, phosphoinositides, "long" β-1,4 galactosyltransferase (GalTase) isoform, Src, as well as the actin cytoskeleton in a spatiotemporal manner. Specialized functions attributed to AKAP12 include the suppression of cancer malignancy, especially aspects of metastatic progression, regulation of blood-brain and blood-retina barrier formation, and resensitization of β2-adrenergic pain receptors. Recent data identify a direct role for AKAP12 in cytokinesis completion, further suggesting a function as a negative regulator of cell senescence. The current review will discuss the emerging knowledge base of AKAP12-related biological roles and how the factors that affect AKAP12 expression or that interact with AKAP12 at the protein level control cancer progression and blood-tissue barrier formation.
新出现的数据表明，SSeCKS/Gravin/AKAP12（“AKAP12”）最初被鉴定为重症肌无力病例中的一种自身抗原，它通过其支架关键信号蛋白的能力来控制多种生物学过程，这些关键信号蛋白如蛋白激酶（PK）C和A、钙调蛋白、细胞周期蛋白、磷酸肌醇、“长”β-1,4半乳糖基转移酶（GalTase）同工型、Src以及肌动蛋白细胞骨架，以时空方式进行调控。归因于AKAP12的特定功能包括抑制癌症恶性肿瘤，尤其是转移进展方面，调节血脑屏障和血视网膜屏障的形成，以及使β2-肾上腺素能疼痛受体重新敏感化。最近的数据确定了AKAP12在胞质分裂完成中的直接作用，进一步表明其作为细胞衰老负调节因子的功能。本综述将讨论与AKAP12相关生物学作用的新兴知识库，以及影响AKAP12表达或在蛋白质水平与AKAP12相互作用的因素如何控制癌症进展和血组织屏障形成。
