TIF1 Proteins in Genome Stability and Cancer

McAvera, Roisin; Crawford, Lisa

doi:10.3390/cancers12082094

Cited by 54 publications

(42 citation statements)

References 100 publications

(183 reference statements)

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“…One such example is represented by Class VI TRIM proteins, for which the mechanism behind the observed cellular E3 ligase activity has remained elusive. This class of TRIMs - which includes TRIM24, TRIM28 (KAP1) and TRIM33 - is best known for its role as transcriptional regulators, a role which appears functionally unrelated to their ubiquitination activity [ 45 , 46 ]. Intriguingly, the isolated RING domains of TRIM24, TRIM28, and TRIM33 were shown to be unable to promote ubiquitin discharge from E2∼Ub conjugates [ 47 ].…”

Section: Trim Ligases With Monomeric Ringsmentioning

confidence: 99%

Does it take two to tango? RING domain self-association and activity in TRIM E3 ubiquitin ligases

Fiorentini

Esposito

Rittinger

2020

Biochemical Society Transactions

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TRIM proteins form a protein family that is characterized by a conserved tripartite motif domain comprising a RING domain, one or two B-box domains and a coiled-coil region. Members of this large protein family are important regulators of numerous cellular functions including innate immune responses, transcriptional regulation and apoptosis. Key to their cellular role is their E3 ligase activity which is conferred by the RING domain. Self-association is an important characteristic of TRIM protein activity and is mediated by homodimerization via the coiled-coil region, and in some cases higher order association via additional domains of the tripartite motif. In many of the TRIM family proteins studied thus far, RING dimerization is an important prerequisite for E3 ligase enzymatic activity though the propensity of RING domains to dimerize differs significantly between different TRIMs and can be influenced by other regions of the protein.

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Section: Trim Ligases With Monomeric Ringsmentioning

confidence: 99%

Does it take two to tango? RING domain self-association and activity in TRIM E3 ubiquitin ligases

Fiorentini

Esposito

Rittinger

2020

Biochemical Society Transactions

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“…Cell de-differentiation and the acquisition of stemness features is mediated by the transcriptional and epigenetic dysregulation of cancer cells [ 8 ]. Among other epigenetic factors, we focused on Tripartite Motif protein 24 TRIM24 (also known as Transcriptional Intermediary Factor 1α, TIF1α), TRIM28 (TIF1β), TRIM33 (TIF1γ), and TRIM66 (TIF1δ) proteins that comprise the Transcriptional Intermediary Factor 1 (TIF1) family of chromatin-binding proteins [ 9 , 10 ]. TIF1 family members act by remodeling chromatin templates and altering the activity of underlying transcriptional mechanisms.…”

Section: Introductionmentioning

confidence: 99%

“…The C-terminal plant homeodomain (PHD) finger and bromodomain (BROMO) unit is present in all TIF1 members and has been demonstrated to be indispensable for transcriptional repression through epigenetic mechanisms. TIF1 proteins can directly interact with modified histones via the PHD–BROMO unit, robustly contributing to the maintenance of genome stability [ 9 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

The Association between TIF1 Family Members and Cancer Stemness in Solid Tumors

Czerwińska

Wlodarczyk

Jaworska

et al. 2021

Cancers

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Cancer progression entails a gradual loss of a differentiated phenotype in parallel with the acquisition of stem cell-like features. Cancer de-differentiation and the acquisition of stemness features are mediated by the transcriptional and epigenetic dysregulation of cancer cells. Here, using publicly available data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases and harnessing several bioinformatic tools, we characterized the association between Transcriptional Intermediary Factor 1 (TIF1) family members and cancer stemness in 27 distinct types of solid tumors. We aimed to define the prognostic value for TIF1 members in predicting a stem cell-like cancer phenotype and patient outcome. Our results demonstrate that high expression of only one member of the TIF1 family, namely TIF1β (also known as Tripartite Motif protein 28, TRIM28) is consequently associated with enriched cancer stemness across the tested solid tumor types, resulting in a worse prognosis for cancer patients. TRIM28 is highly expressed in higher grade tumors that exhibit stem cell-like traits. In contrast to other TIF1 members, only TIF1β/TRIM28-associated gene expression profiles were robustly enriched with stemness markers regardless of the tumor type. Our work demonstrates that TIF1 family members exhibit distinct expression patterns in stem cell-like tumors, despite their structural and functional similarity. Among other TIF1 members, only TRIM28 might serve as a marker of cancer stemness features.

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“…Interestingly, TRIM16, lacking the RING domain, retains E3 ligases activity which is attributable to its RING‐like folded B‐box domain [89] . However, this is not a general feature, as in the case of TRIM66 loss of the RING domain correlates to the absence of ligase activity [90] . Overall, these aspects in the TRIM protein family exhibit nice examples of structure activity relationships in multidomain proteins.…”

Section: Tripartite Motif Proteins: Structural Determinantsmentioning

confidence: 99%

Targeting TRIM Proteins: A Quest towards Drugging an Emerging Protein Class

et al. 2021

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The ubiquitylation machinery regulates several fundamental biological processes from protein homeostasis to a wide variety of cellular signaling pathways. As a consequence, its dysregulation is linked to diseases including cancer, neurodegeneration, and autoimmunity. With this review, we aim to highlight the therapeutic potential of targeting E3 ligases, with a special focus on an emerging class of RING ligases, named tri‐partite motif (TRIM) proteins, whose role as targets for drug development is currently gaining pharmaceutical attention. TRIM proteins exert their catalytic activity as scaffolds involved in many protein–protein interactions, whose multidomains and adapter‐like nature make their druggability very challenging. Herein, we give an overview of the current understanding of this class of single polypeptide RING E3 ligases and discuss potential targeting options.

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TIF1 Proteins in Genome Stability and Cancer

Cited by 54 publications

References 100 publications

Does it take two to tango? RING domain self-association and activity in TRIM E3 ubiquitin ligases

Does it take two to tango? RING domain self-association and activity in TRIM E3 ubiquitin ligases

The Association between TIF1 Family Members and Cancer Stemness in Solid Tumors

Targeting TRIM Proteins: A Quest towards Drugging an Emerging Protein Class

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