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      The Role of Tripartite Motif Family Proteins in TGF-β Signaling Pathway and Cancer

      review-article
      Journal of Cancer Prevention
      Korean Society of Cancer Prevention
      Tripartite motif proteins, Transforming growth factor beta, Neoplasms

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          Abstract

          TGF-β signaling plays a tumor suppressive role in normal and premalignant cells but promotes tumor progression during the late stages of tumor development. The TGF-β signaling pathway is tightly regulated at various levels, including transcriptional and post-translational mechanisms. Ubiquitination of signaling components, such as receptors and Smad proteins is one of the key regulatory mechanisms of TGF-β signaling. Tripartite motif (TRIM) family of proteins is a highly conserved group of E3 ubiquitin ligase proteins that have been implicated in a variety of cellular functions, including cell growth, differentiation, immune response, and carcinogenesis. Recent emerging studies have shown that some TRIM family proteins function as important regulators in tumor initiation and progression. This review summarizes current knowledge of TRIM family proteins regulating the TGF-β signaling pathway with relevance to cancer.

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          Most cited references58

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          Multivalent engagement of chromatin modifications by linked binding modules.

          Various chemical modifications on histones and regions of associated DNA play crucial roles in genome management by binding specific factors that, in turn, serve to alter the structural properties of chromatin. These so-called effector proteins have typically been studied with the biochemist's paring knife--the capacity to recognize specific chromatin modifications has been mapped to an increasing number of domains that frequently appear in the nuclear subset of the proteome, often present in large, multisubunit complexes that bristle with modification-dependent binding potential. We propose that multivalent interactions on a single histone tail and beyond may have a significant, if not dominant, role in chromatin transactions.
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            The role of TGF-β/SMAD4 signaling in cancer

            Transforming growth factor β (TGF-β) signaling pathway plays important roles in many biological processes, including cell growth, differentiation, apoptosis, migration, as well as cancer initiation and progression. SMAD4, which serves as the central mediator of TGF-β signaling, is specifically inactivated in over half of pancreatic duct adenocarcinoma, and varying degrees in many other types of cancers. In the past two decades, multiple studies have revealed that SMAD4 loss on its own does not initiate tumor formation, but can promote tumor progression initiated by other genes, such as KRAS activation in pancreatic duct adenocarcinoma and APC inactivation in colorectal cancer. In other cases, such as skin cancer, loss of SMAD4 plays an important initiating role by disrupting DNA damage response and repair mechanisms and enhance genomic instability, suggesting its distinct roles in different types of tumors. This review lists SMAD4 mutations in various types of cancer and summarizes recent advances on SMAD4 with focuses on the function, signaling pathway, and the possibility of SMAD4 as a prognostic indicator.
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              The PHD finger: implications for chromatin-mediated transcriptional regulation.

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                Author and article information

                Journal
                J Cancer Prev
                J Cancer Prev
                JCP
                Journal of Cancer Prevention
                Korean Society of Cancer Prevention
                2288-3649
                2288-3657
                December 2018
                30 December 2018
                : 23
                : 4
                : 162-169
                Affiliations
                Department of Biochemistry, Lee Gil Ya Cancer and Diabetes Institute, Gachon University College of Medicine, Incheon, Korea
                Author notes
                Correspondence to: Ho-Jae Lee, Department of Biochemistry, Gachon University College of Medicine, 155 Gaetbeol-ro, Yeonsu-gu, Incheon 21999, Korea, Tel: +82-32-899-6054, Fax: +82-32-899-6039, E-mail: hojlee@ 123456gachon.ac.kr , ORCID: Ho-Jae Lee, https://orcid.org/0000-0003-2170-355X
                Article
                jcp-23-162
                10.15430/JCP.2018.23.4.162
                6330992
                30671398
                084b5238-af24-47d7-92cd-caf7e2994526
                Copyright © 2018 Korean Society of Cancer Prevention

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 03 December 2018
                : 18 December 2018
                : 18 December 2018
                Categories
                Review

                tripartite motif proteins,transforming growth factor beta,neoplasms

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