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Cancers 2014, 6(2), 663-683; doi:10.3390/cancers6020663
Review

Structural Pathways of Cytokines May Illuminate Their Roles in Regulation of Cancer Development and Immunotherapy

1
,
1
,
1
,
1
 and
2,3,*
1 Center for Computational Biology and Bioinformatics and College of Engineering, Koc University, Rumelifeneri Yolu, 34450 Sariyer Istanbul, Turkey 2 Cancer and Inflammation Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA 3 Sackler Institute of Molecular Medicine, Department of Human Genetics and Molecular Medicine, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel
* Author to whom correspondence should be addressed.
Received: 26 February 2014 / Revised: 11 March 2014 / Accepted: 12 March 2014 / Published: 25 March 2014
(This article belongs to the Special Issue Cytokines in Cancer)
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Abstract

Cytokines are messengers between tissues and the immune system. They play essential roles in cancer initiation, promotion, metastasis, and immunotherapy. Structural pathways of cytokine signaling which contain their interactions can help understand their action in the tumor microenvironment. Here, our aim is to provide an overview of the role of cytokines in tumor development from a structural perspective. Atomic details of protein-protein interactions can help in understanding how an upstream signal is transduced; how higher-order oligomerization modes of proteins can influence their function; how mutations, inhibitors or antagonists can change cellular consequences; why the same protein can lead to distinct outcomes, and which alternative parallel pathways can take over. They also help to design drugs/inhibitors against proteins de novo or by mimicking natural antagonists as in the case of interferon-γ. Since the structural database (PDB) is limited, structural pathways are largely built from a series of predicted binary protein-protein interactions. Below, to illustrate how protein-protein interactions can help illuminate roles played by cytokines, we model some cytokine interaction complexes exploiting a powerful algorithm (PRotein Interactions by Structural Matching—PRISM).
Keywords: structural pathways; cytokines; structures of cytokines; structural pathways of cytokines; protein interactions; protein interaction prediction; cancer immunotherapy structural pathways; cytokines; structures of cytokines; structural pathways of cytokines; protein interactions; protein interaction prediction; cancer immunotherapy
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Guven-Maiorov, E.; Acuner-Ozbabacan, S.E.; Keskin, O.; Gursoy, A.; Nussinov, R. Structural Pathways of Cytokines May Illuminate Their Roles in Regulation of Cancer Development and Immunotherapy. Cancers 2014, 6, 663-683.

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