Remedy Publications LLC. Annals of Pharmacology and Pharmaceutics 2017 | Volume 2 | Issue 10 | Article 1057 1 Tripartite Motif Proteins - A Protein Family Strongly Linked to Cancer OPEN ACCESS *Correspondence: Christine Blattner, Institute of Toxicology and Genetics, Karlsruhe Institute of Technology, Germany, Fax: +49 (0) 721-608 23354; Tel: +49 (0) 721-608 22634; E-mail: christine.blattner@kit.edu Received Date: 21 Mar 2017 Accepted Date: 30 May 2017 Published Date: 01 Jun 2017 Citation: Elabd S, Andrew C. B. Cato, Christine Blattner. Tripartite Motif Proteins - A Protein Family Strongly Linked to Cancer. Ann Pharmacol Pharm. 2017; 2(10): 1057. Copyright © 2017 Christine Blattner. 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. Short Communication Published: 01 Jun, 2017 Short Communication Cancer is a highly prevalent genetic disease and it is estimated that almost every second person will sufer from the disease during his or her life-time. Despite intensive research over the last 50 years, the development and progression of the disease is, in many cases, still incompletely understood. In the past few years, a distinctive family of proteins called the TRIM (tripartite motif), or RBCC (RING, B-box, coiled-coil region) protein family came into the focus of cancer research. Te TRIM protein family is a very large family of proteins with more than 70 members in humans. All proteins of this family have a tripartite motif in their N-terminus consisting of a RING (really interesting new gene) domain, one or two B-boxes and a coiled-coil region. Te RING domain within their N-terminal RBCC motif is in most cases functional and used by the individual TRIM proteins to polyubiquitinate target proteins followed by their degradation in 26S proteasomes. About half of the members of this large protein family are connected with the development, progression or metastasis of tumors (Figure 1). Many TRIM proteins are overexpressed or down regulated in the diferent cancers (Figure 1) and some TRIM proteins have even been postulated to be prognostic factors or potential therapeutic targets. Despite their widespread association with carcinogenesis, the individual TRIM proteins may difer in the way they exert their efects in cancer. Several TRIM proteins are part of chromosomal rearrangements. For example, TRIM19, also known as PML (promyelocytic leukemia), is fused to the retinoic acid receptor-α in acute promyelocytic leukemia [1] and TRIM24, TRIM27 or TRIM33 are fused to the RET (rearranged during transfection) protein in papillary thyroid carcinoma [2,3]. TRIM24 is also found fused to the fbroblast growth factor receptor 1 in the myeloproliferative syndrome or to the B-Raf protein in hepatocarcinomas [3]. Other chromosomal rearrangements that involve TRIM proteins are the fusion of TRIM4 to the MET kinase in melanomas and the fusion of TRIM46 to MUC1 (Mucin glycoprotein 1) and KRTCAP2 (keratinocyte associated protein 2) in high-grade serous ovarian cancer [4,5]. Other TRIM proteins are involved in carcinogenesis by controlling the abundance and/or the activity of p53, an important tumor suppressor protein [6]. Many of these TRIM proteins reduce p53 level and activity. Among them are TRIM24, TRIM32, TRIM39 and TRIM59, all of which reduce p53 activity by targeting the tumor suppressor protein for proteasomal degradation. TRIM proteins such as TRIM21, TRIM25, TRIM28, TRIM29 also reduce p53 activity but through diferent mechanisms. TRIM21, for instance, indirectly regulates the rapid degradation of p53 by controlling the subcellular localization of the guanine monophosphate synthase (GMPS) and the herpes virus- associated ubiquitin protease (HAUSP). Normally, TRIM21 sequesters GMPS in the cytoplasm through monoubiquitination while HAUSP is localized in the nucleus where it causes degradation of p53 by stabilizing Mdm2, the major ubiquitin ligase for p53. Upon genotoxic stress, TRIM21 is released from GMPS allowing the latter to enter the nucleus to displace Mdm2 from its interaction with p53 and HAUSP, leading to p53 stabilization [7,6]. In another case, TRIM25 suppresses p53 activity by down regulating the activity of p300, a histone acetyl transferase that acetylates p53, a post-translational modifcation that is mandatory for transcriptional activation of several p53 target genes [8,9]. TRIM28, on the other hand, interacts with Mdm2 and promotes Mdm2-mediated ubiquitination and degradation of p53 [10]. In addition, TRIM28 enhances the association of HDAC1 (histone deacetylase 1) and p53 to promote p53 deacetylation [6]. A diferent mechanism is used by TRIM29 that sequesters p53 in the cytoplasm keeping it away from the promoters of its target genes [6]. TRIM29 further promotes the proteasomal degradation of the acetyl transferase Tip60 leading to a decreased acetylation of p53 at lysine 120, a post-translational modifcation that is required for the transcriptional activation of the p53 target genes bax and puma and subsequent initiation of apoptosis [9,11]. TRIM66, one of the few TRIM protein with a non-functional RING Seham Elabd 1,2 , Andrew C. B. Cato 1 and Christine Blattner 1 * 1 Institute of Toxicology and Genetics, Karlsruhe Institute of Technology, Germany 2 Department of Human Physiology, Medical Research Institute, Alexandria University, Egypt