The Ohio State University Comprehensive Cancer Center-James Cancer Hospital and Solove Research Institute, Department of Radiation Oncology, The Ohio State University, Columbus, OH 43210, USA.
Cells. 2022 May 14;11(10):1645. doi: 10.3390/cells11101645.
RALA and RALB are highly homologous small G proteins belonging to the RAS superfamily. Like other small GTPases, the RALs are molecular switches that can be toggled between inactive GDP-bound and active GTP-bound states to regulate diverse and critical cellular functions such as vesicle trafficking, filopodia formation, mitochondrial fission, and cytokinesis. The RAL paralogs are activated and inactivated by a shared set of guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs) and utilize similar sets of downstream effectors. In addition to their important roles in normal cell biology, the RALs are known to be critical mediators of cancer cell survival, invasion, migration, and metastasis. However, despite their substantial similarities, the RALs often display striking functional disparities in cancer. RALA and RALB can have redundant, unique, or even antagonistic functions depending on cancer type. The molecular basis for these discrepancies remains an important unanswered question in the field of cancer biology. In this review we examine the functions of the RAL paralogs in normal cellular physiology and cancer biology with special consideration provided to situations where the roles of RALA and RALB are non-redundant.
RALA 和 RALB 是高度同源的小 G 蛋白，属于 RAS 超家族。与其他小 GTPases 一样，RAL 是分子开关，可以在非活性 GDP 结合状态和活性 GTP 结合状态之间切换，从而调节各种关键的细胞功能，如囊泡运输、丝状伪足形成、线粒体裂变和胞质分裂。RAL 同源物通过一组共享的鸟嘌呤核苷酸交换因子（GEFs）和 GTPase 激活蛋白（GAPs）被激活和失活，并利用类似的下游效应器。除了在正常细胞生物学中的重要作用外，RAL 还被认为是癌细胞存活、侵袭、迁移和转移的关键介质。然而，尽管它们有很大的相似性，但 RAL 在癌症中经常表现出显著的功能差异。RALA 和 RALB 可以根据癌症类型具有冗余、独特甚至拮抗的功能。这些差异的分子基础仍然是癌症生物学领域一个重要的未解决问题。在这篇综述中，我们研究了 RAL 同源物在正常细胞生理学和癌症生物学中的功能，并特别考虑了 RALA 和 RALB 作用非冗余的情况。
