具有轉(zhuǎn)化作用的生長因子- beta (TGF-beta) 超級家族是一個涉及包括發(fā)育、傷口愈合及細(xì)胞增殖和存活等諸多生物學(xué)過程的細(xì)胞外配體的大家族,。由于這些蛋白質(zhì)可以兼具促進(jìn)生長和抑制生長的作用,因此人們認(rèn)為它們既參與腫瘤的發(fā)生和轉(zhuǎn)移的過程又參與防止這些病理表現(xiàn)型出現(xiàn)的過程。
2008 年 11 月 18 日發(fā)表的Science Signaling專刊著重介紹了有關(guān) TGF-beta 信號的傳導(dǎo)以及該通路與其它信號傳導(dǎo)通路的交叉點的最新的見解,。由 L. L. Hoover 和 S. W. Kubalak撰寫的一篇 Perspective 討論了 Smad 族蛋白的非經(jīng)典的角色。該組蛋白質(zhì)原先被認(rèn)作是 TGF-beta 信號中的關(guān)鍵性的傳感器,。在另外一篇中,, F. Liu 就發(fā)現(xiàn) PCTA 是 TGF-beta 信號傳導(dǎo)中的一個調(diào)節(jié)因子的最近的研究進(jìn)行了討論。這種蛋白質(zhì)可促進(jìn) TGF-beta 所介導(dǎo)的轉(zhuǎn)錄調(diào)節(jié)和生長抑制,。最后,,在中,, N. R. Gough 報道了最近舉行的為時一日的一場研討會,。該研討會介紹了有關(guān) TGF-beta 信號傳導(dǎo)的令人感興趣的新的方面,,并從歷史的角度來觀察這一分子及其家族成員的取決于所處環(huán)境的信號傳導(dǎo)的概念以及其是如何增進(jìn)我們對諸如癌癥等疾病的理解的。(生物谷Bioon.com)
生物谷推薦原始出處:
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.