Roles of Tristetraprolin in Tumorigenesis

Park, Jeong-Min; Lee, Tae-Hee; Kang, Tae-Hong

doi:10.3390/ijms19113384

Cited by 46 publications

(42 citation statements)

References 133 publications

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“…Stabilization by shielding from RNA decay-promoting proteins [55] lncRNA-HGBC Stabilization by shielding from RNA decay-promoting proteins [56] lncRNA-p21 Promotion of degradation by recruitment of let7-Ago2 [57] HOTAIR Promotion of degradation by recruitment of let7-Ago2 [58] RMRP Facilitation of nuclear export via interaction with CRM1 [59] Serine/arginine-rich splicing factor 1 (SRSF1) NEAT1 Stabilization by an unknown mechanism [60] Arginine/uridine-rich RNA element (ARE)/poly(U)-binding/degradation factor 1 (AUF1) NEAT1 Destabilization, probably by recruitment of a deadenylase complex [61] Polyadenylate-binding protein 1 (PABPN1) NEAT1 Promotion of degradation by recruitment of NEXT-exosome [62,63] TUG1 Promotion of degradation by recruitment of NEXT-exosome [62,63] Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) HULC Promotion of degradation by recruitment of the deadenylase complex CCR4-NOT via CNOT1 [64] H19 Targeting of lamellipodia and perinuclear regions [65] Tristetraprolin (TTP) HOTAIR Promotion of degradation, most likely by recruitment of the deadenylase complex CCR4-NOT [66,67] G-rich RNA sequence-binding factor 1 (GRSF1) RMRP Retention in the mitochondrial matrix by an unknown mechanism [68] Heterogeneous nuclear ribonucleoprotein K (hnRNPK) MALAT1 Retention in the nucleus by an unknown mechanism [69,70]…”

Section: Neat1mentioning

confidence: 99%

“…Besides the two previously discussed examples HuR and AUF1, TTP is another RBP that binds to AREs, adenylate/uridylate-rich RNA motifs that function as signals for the rapid degradation of RNA [61,66,[71][72][73]85,91]. While HuR promotes the stability of RNAs by shielding these recognition sites, AUF1 recruits, upon binding to AREs, components of the RNA degradation machinery [71][72][73]91].…”

Section: Tristetraprolin (Ttp)mentioning

confidence: 99%

“…In case of TTP, on the other hand, it is well documented that it interacts with CCR4-NOT, one of the two major deadenylase complexes responsible for RNA decay, as well as with PM/Scl-75, a component of the exosome [66]. In addition, TTP also interacts with PABPN1, thereby interfering with polyadenylation, and is involved in mRNA decapping [66]. In summary, TTP destabilizes its RNA targets via multiple different pathways [66].…”

Section: Tristetraprolin (Ttp)mentioning

confidence: 99%

“…In addition, TTP also interacts with PABPN1, thereby interfering with polyadenylation, and is involved in mRNA decapping [66]. In summary, TTP destabilizes its RNA targets via multiple different pathways [66]. As there are numerous oncogenes amongst the targets of TTP, it is generally regarded as a tumor suppressor [66].…”

Section: Tristetraprolin (Ttp)mentioning

confidence: 99%

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RNA-Binding Proteins as Important Regulators of Long Non-Coding RNAs in Cancer

Jonas

Calin

Pichler

2020

IJMS

103

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The majority of the genome is transcribed into pieces of non-(protein) coding RNA, among which long non-coding RNAs (lncRNAs) constitute a large group of particularly versatile molecules that govern basic cellular processes including transcription, splicing, RNA stability, and translation. The frequent deregulation of numerous lncRNAs in cancer is known to contribute to virtually all hallmarks of cancer. An important regulatory mechanism of lncRNAs is the post-transcriptional regulation mediated by RNA-binding proteins (RBPs). So far, however, only a small number of known cancer-associated lncRNAs have been found to be regulated by the interaction with RBPs like human antigen R (HuR), ARE/poly(U)-binding/degradation factor 1 (AUF1), insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1), and tristetraprolin (TTP). These RBPs regulate, by various means, two aspects in particular, namely the stability and the localization of lncRNAs. Importantly, these RBPs themselves are commonly deregulated in cancer and might thus play a major role in the deregulation of cancer-related lncRNAs. There are, however, still many open questions, for example regarding the context specificity of these regulatory mechanisms that, in part, is based on the synergistic or competitive interaction between different RBPs. There is also a lack of knowledge on how RBPs facilitate the transport of lncRNAs between different cellular compartments. Compared to protein-coding genes, lncRNAs are poorly conserved between different species and their expression levels are rather low [7,8]. Initially, this led to the belief that they were nothing but transcriptional noise [6][7][8]. Soon, however, it was discovered that lncRNAs do exhibit considerable functionality, for example as regulators of transcription [6][7][8]. Mechanisms of transcriptional regulation by lncRNAs are multifarious and can occur either in cis or in trans, meaning either closer to or further away from the lncRNA's site of transcription, respectively [6,7]. A frequent mechanism of transcriptional regulation via lncRNAs is the recruitment, or prevention of such, of components of chromatin or histone-modifying complexes, like polycomb repressive complexes or histone deacetylase complexes [11][12][13]. LncRNAs can also direct transcription factors or cofactors to promoter regions of genes and facilitate the formation of chromatin loops between distant enhancers and promoters, as observed for some eRNAs [9,[14][15][16][17]. Another way that they can impact transcription is by interfering with the RNA polymerase II transcription machinery, thereby blocking transcriptional initiation or elongation [18]. LncRNAs are important regulators not only at the level of transcription but also at the post-transcriptional level [6,7]. They regulate pre-mRNA splicing by interacting with splicing factors or with the mRNA itself [19][20][21][22]. A well-studied example for this is metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), an lncRNA that interacts with serine/arginine (SR) spl...

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Section: Neat1mentioning

confidence: 99%

Section: Tristetraprolin (Ttp)mentioning

confidence: 99%

Section: Tristetraprolin (Ttp)mentioning

confidence: 99%

Section: Tristetraprolin (Ttp)mentioning

confidence: 99%

See 2 more Smart Citations

RNA-Binding Proteins as Important Regulators of Long Non-Coding RNAs in Cancer

Jonas

Calin

Pichler

2020

IJMS

103

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“…The purpose of this review is to summarize recent evidence from our laboratory and others on several aspects of this protein domain, including: Its key amino acid residues as applied to its predicted structure and RNA binding; the apparent continued evolution of this domain in some lineages; the concept of interchangeability of this domain among very distant species; the possibilities of regulation of RNA binding by protein modification; and the proposal that all aspects of protein function can be abrogated by point mutations in the TZF domain that prevent RNA binding. For more general recent discussions of the proteins of this family, the reader is referred to the following reviews (Baou, Jewell, & Murphy, ; Brooks & Blackshear, ; Guo, Wang, Jiang, Xia, & Jin, ; Gupta et al, ; Maeda & Akira, ; Park, Lee, & Kang, ; Prabhala & Ammit, ; Ross, Brennan‐Laun, & Wilson, ; Sanduja, Blanco, Young, Kaza, & Dixon, ; Wells et al, ; Zanocco‐Marani, ). For discussions of zinc fingers in general, see the following reviews: (Abbehausen, ; Cassandri et al, ; Fu & Blackshear, ; Klug, ; Laity, Lee, & Wright, ).…”

Section: Introductionmentioning

confidence: 99%

The tandem zinc finger RNA binding domain of members of the tristetraprolin protein family

et al. 2019

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Tristetraprolin (TTP), the prototype member of the protein family of the same name, was originally discovered as the product of a rapidly inducible gene in mouse cells. Development of a knockout (KO) mouse established that absence of the protein led to a severe inflammatory syndrome, due in part to elevated levels of tumor necrosis factor (TNF). TTP was found to bind directly and with high affinity to specific AU‐rich sequences in the 3′‐untranslated region of the TNF mRNA. This initial binding led to promotion of TNF mRNA decay and inhibition of its translation. Many additional TTP target mRNAs have since been identified, some of which are cytokines and chemokines involved in the inflammatory response. There are three other proteins in the mouse with similar activities and domain structures, but whose KO phenotypes are remarkably different. Moreover, proteins with similar domain structures and activities have been found throughout eukaryotes, demonstrating that this protein family arose from an ancient ancestor. The defining characteristic of this protein family is the tandem zinc finger (TZF) domain, a 64 amino acid sequence with many conserved residues that is responsible for the direct RNA binding. We discuss here many aspects of this protein domain that have been elucidated since the original discovery of TTP, including its sequence conservation throughout eukarya; its apparent continued evolution in some lineages; its functional dependence on many key conserved residues; its “interchangeability” among evolutionarily distant species; and the evidence that RNA binding is required for the physiological functions of the proteins. This article is categorized under: RNA Interactions with Proteins and Other Molecules > RNA‐Protein Complexes RNA Interactions with Proteins and Other Molecules > Protein–RNA Recognition RNA Interactions with Proteins and Other Molecules > Protein–RNA Interactions: Functional Implications

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Kinome inhibition reveals a role for polo‐like kinase 1 in targeting post‐transcriptional control in cancer

et al. 2021

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Dysfunctions in post-transcriptional control are observed in cancer and chronic inflammatory diseases. Here, we employed a kinome inhibitor library (n=378) in a reporter system selective for 3-untranslated region-AU-rich elements (ARE). Fifteen inhibitors reduced the ARE reporter activity; among the targets is the polo-like kinase 1 (PLK1). RNAseq experiments demonstrated that the PLK1 inhibitor, volasertib, reduces the expression of cytokine and cell growth ARE-mRNAs. PLK1 inhibition caused accelerated mRNA decay in cancer cells and was associated with reduced phosphorylation and stability of the mRNA decay-promoting protein, tristetraprolin (ZFP36/TTP). Ectopic expression of PLK1 increased abundance and stability of high molecular weight of ZFP36/TTP likely of the phosphorylated form. PLK1 effect was associated with the MAPK-MK2 pathway, a major regulator of ARE-mRNA stability, as evident from MK2 inhibition, in vitro phosphorylation, and knockout experiments. Mutational analysis demonstrates that TTP serine 186 is a target for PLK1 effect. Treatment of mice with the PLK1 inhibitor reduced both ZFP36/TTP phosphorylation in xenograft tumor tissues, and the tumor size. In cancer patients' tissues, PLK1/ARE-regulated gene cluster was overexpressed in solid tumors and associated with poor survival. The data showed that PLK1-mediated posttranscriptional aberration could be a therapeutic target.

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Roles of Tristetraprolin in Tumorigenesis

Cited by 46 publications

References 133 publications

RNA-Binding Proteins as Important Regulators of Long Non-Coding RNAs in Cancer

RNA-Binding Proteins as Important Regulators of Long Non-Coding RNAs in Cancer

The tandem zinc finger RNA binding domain of members of the tristetraprolin protein family

Kinome inhibition reveals a role for polo‐like kinase 1 in targeting post‐transcriptional control in cancer

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