具有转化作用的生长因子- beta (TGF-beta) 超级家族是一个涉及包括发育、伤口愈合及细胞增殖和存活等诸多生物学过程的细胞外配体的大家族。由于这些蛋白质可以兼具促进生长和抑制生长的作用，因此人们认为它们既参与肿瘤的发生和转移的过程又参与防止这些病理表现型出现的过程。
2008 年 11 月 18 日发表的Science Signaling专刊着重介绍了有关 TGF-beta 信号的传导以及该通路与其它信号传导通路的交叉点的最新的见解。由 L. L. Hoover 和 S. W. Kubalak撰写的一篇 Perspective 讨论了 Smad 族蛋白的非经典的角色。该组蛋白质原先被认作是 TGF-beta 信号中的关键性的传感器。在另外一篇中， F. Liu 就发现 PCTA 是 TGF-beta 信号传导中的一个调节因子的最近的研究进行了讨论。这种蛋白质可促进 TGF-beta 所介导的转录调节和生长抑制。最后，在中， N. R. Gough 报道了最近举行的为时一日的一场研讨会。该研讨会介绍了有关 TGF-beta 信号传导的令人感兴趣的新的方面，并从历史的角度来观察这一分子及其家族成员的取决于所处环境的信号传导的概念以及其是如何增进我们对诸如癌症等疾病的理解的。（生物谷Bioon.com）
生物谷推荐原始出处：
Sci. Signal., 18 November 2008 Vol. 1,[DOI: 10.1126/scisignal.146pe48]
Holding Their Own: The Noncanonical Roles of Smad Proteins
Loretta L. Hoover and Steven W. Kubalak*
Department of Cell Biology and Anatomy, Cardiovascular Developmental Biology Center, Medical University of South Carolina, Charleston, SC 29425, USA.
Abstract: The identification of Smads as protein transcription factors in 1995 led to elucidation of the canonical transforming growth factor–β (TGF-β) signaling pathway. In the years that have followed, nuances of the pathway have been realized, and the once-simple scheme of ligand to receptor to activated transcription factor is now understood to be highly regulated at each step and riddled with crosstalk from other pathways. The Smads are also recognized as important players outside of canonical TGF-β–dependent signaling and are responsible for regulating diverse cellular processes. New evidence suggests that Smad7 plays an integral role in maintaining cell-cell adhesion through direct regulation of β-catenin. Receptor-activated Smads regulate the processing of a subset of microRNAs, particularly miR-21. The number of reports demonstrating the interactions of Smads with proteins outside of canonical TGF-β signaling is increasing, although the functional relevance of these interactions is not known. Investigating these interactions will likely yield more evidence that Smads serve important and diverse purposes beyond their original reported function as signal transducers in the TGF-β pathway.
Sci. Signal., 18 November 2008[DOI: 10.1126/scisignal.146pe49]
PCTA: A New Player in TGF-β Signaling
Fang Liu*
Center for Advanced Biotechnology and Medicine, Rutgers, The State University of New Jersey, 679 Hoes Lane, Piscataway, NJ 08854, USA. Susan Lehman Cullman Laboratory for Cancer Research, Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 164 Frelinghuysen Road, Piscataway, NJ 08854, USA. Cancer Institute of New Jersey, 195 Little Albany Street, New Brunswick, NJ 08903, USA.
Abstract: Transforming growth factor β (TGF-β) regulates a wide variety of biological activities by binding to cell surface serine/threonine kinase receptors. Canonical TGF-β signaling is mediated by Smad proteins, which transduce the TGF-β signal from the cell surface into the nucleus to regulate transcription. Upon TGF-β binding and receptor activation, the TGF-β receptor phosphorylates Smad2 and Smad3. SARA (Smad anchor for receptor activation) and cPML (cytoplasmic promyelocytic leukemia protein) recruit Smad2 and Smad3 for phosphorylation by the TGF-β receptor. cPML is sequestered in the nucleus by the homeodomain protein TGIF (TG-interacting factor), a negative regulator of TGF-β signaling. Recently, PCTA (PML competitor for TGIF association) has been shown to compete with cPML for binding to TGIF, resulting in the accumulation of cPML in the cytoplasm, where it mediates the interaction between Smad2/3 and SARA and coordinates the phosphorylation of Smad2 and Smad3 by the TGF-β receptor. Accordingly, PCTA promotes TGF-β–mediated transcriptional regulation and growth inhibition. Thus, PCTA defines a new regulator in TGF-β signaling.
Highlights from a TGF-β Workshop
18 November 2008
Nancy R. Gough
TGF-β: Discovery and Promise-- A Symposium Honoring the Memory of Anita B. Roberts
This one-day symposium was held at the Natcher Conference Center at the NIH campus in Bethesda, Maryland, on 19 September 2008. With over 400 registrants and 13 speakers, as well as more than 35 posters, this short meeting was packed with interesting science. The symposium was organized by Kathleen Flanders (National Cancer Institute), Michael Sporn (Dartmouth Medical School) and Lopa Mishra (Georgetown University). The attendees and speakers came from all over the world, including Japan (Kohei Miyazono), Germany (Klaus Unsicker), and the Netherlands (Peter ten Dijke). Many, if not all, of the invited speakers had worked, collaborated, or wrote articles with Anita Roberts (1942-2006) and most included anecdotes and praise for the colleague, scientist, friend, and mentor that she was. Several talks are highlighted here.
