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.

中文翻译：

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RIT1 的分子功能及其对人类疾病的贡献。

RIT1 是 GTPases Ras 家族的成员，通过严格控制的信号网络指导广泛的细胞生理反应。典型的 Ras GTP 酶是 RAF/MEK/ERK 通路的明确调节因子，这些突变在癌症和一类称为 RASopathies 的发育障碍中具有致病性。现在新出现的临床证据已经证明 RIT1 在 RASopathies（即 Noonan 综合征）以及包括肺腺癌和骨髓恶性肿瘤在内的各种癌症中发挥作用。虽然 RIT1 主要是在神经元分化和存活的背景下描述的，但异常 RIT1 介导的信号传导背后的机制仍然难以捉摸。在这里，我们将回顾在分子、细胞和有机体水平上表征 RIT1 GTPase 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 的生物学功能并深入了解其致病机制对于为 RIT1 突变型努南综合征和癌症患者开发有效的治疗干预措施至关重要。