Beyond its well-known canonical function as a tumor suppressor, p53 is also involved in numerous cellular processes through altered transcription under both normal and pathological conditions. The functional diversity of p53 outputs is complex and dependent on cell context. However, the underlying mechanisms responsible for this diversity remain largely unclear. The emerging evidence of p53 mutations involved in regulating endocytic trafficking and signaling, in tandem to promote malignancy (invasion, exosome biogenesis and immune evasion), sheds light on possible mechanisms behind the p53-driven complexity. The interrelated nature of endocytic trafficking and receptor signaling that form dynamic and adaptable feedback loops – either positive or negative – functions to modulate multiple cellular outputs. Biasing the tunable endocytic trafficking and receptor signaling network by mutant p53 expands the purview of p53, allowing its contribution to diverse and aggressive phenotypes. In this review, we explore recent studies in which the novel role of mutant p53 in altering endocytic trafficking to bias receptor signaling and drive transforming phenotypes is revealed. Understanding the complex crosstalk of mutant p53, endocytic trafficking and receptor signaling will allow the development of therapies to selectively target p53-altered endocytic processes.

除了众所周知的作为肿瘤抑制因子的典型功能之外，p53 还通过在正常和病理条件下改变转录参与许多细胞过程。p53 输出的功能多样性很复杂，取决于细胞环境。然而，导致这种多样性的潜在机制在很大程度上仍不清楚。p53 突变参与调节内吞运输和信号传导，同时促进恶性肿瘤（入侵、外泌体生物发生和免疫逃避）的新证据揭示了 p53 驱动的复杂性背后的可能机制。内吞运输和受体信号传导的相互关联性质形成动态和适应性反馈回路 - 无论是正面还是负面 - 用于调节多个细胞输出。通过突变 p53 偏向可调内吞运输和受体信号网络，扩大了 p53 的范围，使其对多样化和侵略性表型的贡献。在这篇综述中，我们探索了最近的研究，其中揭示了突变体 p53 在改变内吞运输以偏向受体信号和驱动转化表型方面的新作用。了解突变 p53、内吞运输和受体信号转导的复杂串扰，将有助于开发选择性靶向 p53 改变的内吞过程的疗法。我们探索了最近的研究，其中揭示了突变 p53 在改变内吞运输以偏向受体信号和驱动转化表型方面的新作用。了解突变 p53、内吞运输和受体信号转导的复杂串扰，将有助于开发选择性靶向 p53 改变的内吞过程的疗法。我们探索了最近的研究，其中揭示了突变 p53 在改变内吞运输以偏向受体信号和驱动转化表型方面的新作用。了解突变 p53、内吞运输和受体信号转导的复杂串扰，将有助于开发选择性靶向 p53 改变的内吞过程的疗法。