Specificity of Smad Proteins in Transforming Growth Factor-beta Signaling

转化生长因子-β（TGF-β）调节一系列迷人的细胞过程，包括细胞增殖、分化、迁移、组织和死亡，以及影响广泛的生物学功能，如胚胎发育、造血和免疫及炎症反应。鉴于TGF-β作用的多功能性质，TGF-β功能的破坏与许多人类疾病有关，特别是结肠直肠癌和胰腺癌，这并不奇怪。Smad蛋白（共有10种）是TGF-β细胞作用的关键成分。事实上，Smad 4也被称为DPC 4，因为在胰腺癌中缺失了第4位点。该项目解决了每个Smad蛋白如何在细胞中在分子水平上工作，以及它调节生物功能的哪一部分。总的来说，该项目的成果可能为治疗TGF-β相关疾病（如结直肠癌和胰腺癌）提供明确和特异性的分子靶点。

Transforming growth factor-betas (TGF-beta) regulate a fascinating array of cellular processes including cell proliferation, differentiation, migration, organization and death, as well as affect a wide range of biological functions, such as embryonic development, hematopoiesis and immune and inflammatory responses. Given the multifunctional nature of TGF-beta action, it is not surprising that the disruptions of TGF-beta functions have been implicated in many human disorders, particularly in colorectal and pancreatic cancers. The Smad proteins (there are ten of them) are critical components of TGF-beta cellular actions. In fact, Smad4 also called DPC4 for deleted in pancreatic carcinoma locus 4. This project addresses how each Smad protein works at molecular level in the cell, and which part of biological functions it regulates. Collectively, the outcomes of the project may provide clear and specific molecular targets to treat TGF-beta related diseases such as colorectal and pancreatic cancers.