The role of TRIM family proteins in the regulation of cancer stem cell self-renewal

Abstract

The tripartite-motif (TRIM) family of proteins represents one of the largest classes of putative single protein RING-finger E3 ubiquitin ligases. The members of this family are characterized by an N-terminal TRIM motif containing one RING-finger domain, one or two zinc-finger domains called B boxes (B1 box and B2 box), and a coiled-coil region.The TRIM motif can be found in isolation or in combination with a variety of C-terminal domains, and based on C-terminus, TRIM proteins are classified into 11 distinct groups.Because of the complex nature of TRIM proteins, they are implicated in a variety of cellular functions and biological processes, including regulation of cell proliferation, cell division and developmental processes, cancer transformation, regulation of cell metabolism, autophagocytosis, modification of chromatin status, regulation of gene transcription, post-translational modifications, and interactions with pathogens. Here, we demonstrate the specific activities of TRIM family proteins that contribute to the cancer stem cell phenotype. A growing body of evidence demonstrates that several TRIM members guarantee the acquisition of stem cell properties and the ability to sustain stem-like phenotype by cancer cells using distinct mechanisms. For other members, further work is needed to understand their full contribution to stem cell self-renewal.Identification of TRIM proteins that possess the potential to serve as therapeutic targets may result in the development of new therapeutic strategies. Finally, these strategies may result in the disruption of the machinery of stemness acquisition, which may prevent tumor growth, progression, and overcome the resistance to anticancer therapies. K E Y W O R D Scancer, pluripotency, RING, self-renewal, stem cells, TRIM

Learning Cell-Type-Specific Gene Regulation Mechanisms by Multi-Attention Based Deep Learning With Regulatory Latent Space

“…It belongs to the Tripartite motif (TRIM) family which is related to the cancer stem cell self-renewal process. TRIM6 , more specifically, directly interacts with the MYC gene to modulate stem cell differentiation (Jaworska et al, 2019 ). Attention weights of TF were relatively higher than the weights of ME.…”

TRIM31 promotes acute myeloid leukemia progression and sensitivity to daunorubicin through the Wnt/β-catenin signaling

“…Due to the specific nature of TRIM proteins, they have been found to be implicated in a variety of biological processes, such as cell proliferation, cell division and developmental processes and cell metabolism [13]. A growing body of evidence shows that several TRIM members are involved in the tumorigenesis and serve as therapeutic targets for the treatment of cancers [14]. Additionally, several TRIM proteins have been found to be involved in blood cancers, including acute promyelocytic leukemia (APL), B-cell acute lymphocytic leukemia (B-ALL), chronic lymphocytic leukemia (CLL), chronic myeloid leukemia (CML), chronic myelomonocytic leukemia (CMML) and AML [15][16][17][18].…”

The Tripartite Nexus: Autophagy, Cancer, and Tripartite Motif-Containing Protein Family Members

“…Several TRIMs can regulate pathways seminal to cancer stemness including STAT signaling, AKT signaling, NANOG-Sox2-Oct-3/4 networks, and pathways related to epithelialmesenchymal transition (EMT). In this section we cite a few examples of how TRIMs can regulate stemness, a topic that was recently reviewed by Jaworska et al (2020). TRIM28 is reported to maintain of Oct-3/4-Sox2-NANOG expression in breast cancer cells (Czerwinska et al, 2017).…”