The molecular functions of RIT1 and its contribution to human disease.
The molecular functions of RIT1 and its contribution to human disease.
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DOI：
10.1042/bcj20200442
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发表时间：
2020-08-14
期刊：
影响因子：
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通讯作者：
McCormick F
中科院分区：
文献类型：
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作者：
Van R;Cuevas-Navarro A;Castel P;McCormick F
RIT1是Ras家族GTP酶家族的成员，通过严格控制的信号网络引导广泛的细胞生理反应。典型的RAS GTP酶是RAF/MEK/ERK途径的明确调节者，这些酶的突变是癌症和一类称为Rasopathies的发育障碍的致病因素。新出现的临床证据表明，RIT1在Rasopathies，即Noonan综合征，以及包括肺腺癌和髓系恶性肿瘤在内的各种癌症中发挥作用。虽然RIT1主要在神经元分化和存活的背景下被描述，但RIT1介导的异常信号传递的机制仍然难以捉摸。在这里，我们将回顾为在分子、细胞和生物水平上表征RIT1 GTP酶的生化和功能特性所做的努力，并提供由RIT1突变引起的不同人类状况的表型概述。深入了解RIT1的生物学功能和对其致病机制的认识对于开发有效的治疗RIT1突变Noonan综合征和癌症的干预措施是必不可少的。
RIT1 is a member of the Ras family of GTPases that direct broad cellular physiological responses through tightly controlled signaling networks. The canonical Ras GTPases are well-defined regulators of the RAF/MEK/ERK pathway and mutations in these are pathogenic in cancer and a class of developmental disorders termed RASopathies. Emerging clinical evidences have now demonstrated a role for RIT1 in RASopathies, namely Noonan syndrome, and various cancers including lung adenocarcinoma and myeloid malignancies. While RIT1 has been mostly described in the context of neuronal differentiation and survival, the mechanisms underlying aberrant RIT1-mediated signaling remain elusive. Here, we will review efforts undertaken to characterize the biochemical and functional properties of the RIT1 GTPase at the molecular, cellular, and organismal level, as well as provide a phenotypic overview of different human conditions caused by RIT1 mutations. Deeper understanding of RIT1 biological function and insight to its pathogenic mechanisms are imperative to developing effective therapeutic interventions for patients with RIT1-mutant Noonan syndrome and cancer.