Clements Christopher M, Henen Morkos A, Vögeli Beat, Shellman Yiqun G
Department of Dermatology, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Department of Biochemistry and Molecular Genetics, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Cancers (Basel). 2023 Jun 1;15(11):3019. doi: 10.3390/cancers15113019.
SAM domains are crucial mediators of diverse interactions, including those important for tumorigenesis or metastasis of cancers, and thus SAM domains can be attractive targets for developing cancer therapies. This review aims to explore the literature, especially on the recent findings of the structural dynamics, regulation, and functions of SAM domains in proteins containing more than one SAM (multi-SAM containing proteins, MSCPs). The topics here include how intrinsic disorder of some SAMs and an additional SAM domain in MSCPs increase the complexity of their interactions and oligomerization arrangements. Many similarities exist among these MSCPs, including their effects on cancer cell adhesion, migration, and metastasis. In addition, they are all involved in some types of receptor-mediated signaling and neurology-related functions or diseases, although the specific receptors and functions vary. This review also provides a simple outline of methods for studying protein domains, which may help non-structural biologists to reach out and build new collaborations to study their favorite protein domains/regions. Overall, this review aims to provide representative examples of various scenarios that may provide clues to better understand the roles of SAM domains and MSCPs in cancer in general.
SAM结构域是多种相互作用的关键介导因子，包括对癌症发生或转移至关重要的那些相互作用，因此SAM结构域可能是开发癌症治疗方法的有吸引力的靶点。本综述旨在探索相关文献，特别是关于含有多个SAM结构域的蛋白质（多SAM结构域蛋白，MSCPs）中SAM结构域的结构动力学、调控及功能的最新研究结果。这里讨论的主题包括一些SAM结构域的内在无序性以及MSCPs中的另一个SAM结构域如何增加其相互作用和寡聚化排列的复杂性。这些MSCPs之间存在许多相似之处，包括它们对癌细胞黏附、迁移和转移的影响。此外，它们都参与某些类型的受体介导信号传导以及神经学相关功能或疾病，尽管具体的受体和功能有所不同。本综述还提供了研究蛋白质结构域方法的简要概述，这可能有助于非结构生物学家拓展并建立新的合作关系，以研究他们感兴趣的蛋白质结构域/区域。总体而言，本综述旨在提供各种情况的代表性实例，这些实例可能为更好地理解SAM结构域和MSCPs在癌症中的一般作用提供线索。
