The CCR4-NOT complex is a tumor suppressor in Drosophila melanogaster eye cancer models

Vicente, Carmen; Stirparo, Rocco; Demeyer, Sofie; Bock, Charles E. de; Gielen, Olga; Atkins, Mardelle; Yan, Jiekun; Halder, Georg; Hassan, Bassem A.; Cools, Jan

doi:10.1186/s13045-018-0650-0

Cited by 15 publications

(16 citation statements)

References 43 publications

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“…The situation in yeast may be conserved in other organisms, including humans. Notably in this regard, the Ccr4-Not complex in human cells was recently implicated in cancer development ( Allison, 2017 ; Maolake et al, 2017 ; Vicente et al, 2018 ). Accordingly, it would be worthwhile to determine whether p21 is involved in a similar control mechanism in human cells.…”

Section: Resultsmentioning

confidence: 99%

Dual Repressive Function by Cip1, a Budding Yeast Analog of p21, in Cell-Cycle START Regulation

Liu

Hao

et al. 2020

Front. Microbiol.

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Cip1, a newly identified yeast analog of p21, is a Cln3-CDK inhibitor that negatively regulates cell-cycle START. However, its function remains poorly understood. In this study, we found that deletion of CLN3 did not result in bypass of G1-phase arrest caused by Cip1 overexpression. Cip1 depletion in cln3 -null mutants significantly advanced the timing of Cln2 expression, supporting the idea that Cip1 represses START in a Cln3-independent manner. We set to search for novel Cip1 interacting proteins and found that Ccr4, a known START regulator, and its associated factor Caf120, interact with Cip1. Ccr4-Caf120 acts redundantly with Cdk1-Cln3 to inhibit Whi5-mediated regulation of START. This interaction was conserved between human Ccr4 and p21. In addition, deletion of WHI5 robustly suppressed G1-phase arrest caused by Cip1 overexpression. We conclude that Cip1 negatively regulates START by acting as a dual repressor of Ccr4 in parallel with Cln3.

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Section: Resultsmentioning

confidence: 99%

Dual Repressive Function by Cip1, a Budding Yeast Analog of p21, in Cell-Cycle START Regulation

Liu

Hao

et al. 2020

Front. Microbiol.

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“…We, therefore, hypothesize that the interaction between CcGASA4 and PRPBAG6-A, also a PRP, may be similarly involved in defense in Citrus. CNOT3 is a component of the CCR4-NOT complex, an essential and conserved multi-subunit complex that plays multiple roles, including suppressing tumors in drosophila and in humans, maintaining selfrenewal program in ES cells, and regulating RNA turnover and transcription termination (Vicente et al 2018;Martufi 2014). Because CNOT3 interacts with Nucleolin and Histone H1 (Martufi 2014), GASA4′s nuclear localization and its interaction with CNOT3 may signify its potential role in chromatin organization.…”

Section: Discussionmentioning

confidence: 99%

Molecular characterization of the gibberellin-stimulated transcript of GASA4 in Citrus

Cheng

Zhong

et al. 2020

Plant Growth Regul

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A Citrus clementina gene, CcGASA4, which is involved in the responses of citrus to stress, was characterized. The gene was induced by Citrus tristeza virus infection, wounding and gibberellic, salicylic and abscisic acid treatments. A qRT-PCR analysis showed that CcGASA4 had a very high basal expression in flowers yet was still able to be further induced independently in giberellic, salicylic and abscisic acid-treated flowers. Subcellular localization analysis revealed that the CcGASA4 protein localized to the cell membrane and nucleus. A yeast two-hybrid analysis and bimolecular fluorescence complementation (BiFC) assays showed that CcGASA4 interacted with two proteins, the large proline-rich protein bag6-A (PRPBAG6-A) and the general negative regulator of transcription subunit 3 (CNOT3). PRPBAG6 has been reported to be involved in disease resistance. Replacing some of CcGASA4's conserved cysteines with alanines (Cys → Ala) abolished the protein's interaction with CNOT3 but did not show any effect on the protein's interaction with PRPBAG6-A. Thus, CcGASA4 appears to play multiple roles in Citrus, probably by interacting with different proteins and/or by localizing to different subcellular compartments.

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“…Thus, we identified 25 RBPs (Fig. 6B): 5 never studied in cancer (CSTF2T, SRRM1, CPSF7, EIF4G3, and ELOA), 6 associated with other cancer types (TNRC6B 62 , SEC31A 63 , SPTAN1 64 , MARK2 65 , TNRC6A 66 , and PMS1 67 ), 7 associated with BC (CASC3 68 , HNRNPF 69 , MYH9 70 TLN1 71 , DDX5 72 , TAF15 73 , and EIF4G1 74 ), 3 already described as tumor suppressors in BC (CTNND1 23 , LIMA1 24 , AATF 25 ), and 4 identified as tumor suppressors in other cancer types (MEX3C 75 , UPF1 76 , CNOT1 77 , and TNKS1BP1 78 ).…”

Section: Resultsmentioning

confidence: 99%

“…Although most of the proteins identified have been associated with breast and other cancer types, their suppressive roles remain undetermined 62–74 . Only 3 have been described as tumor suppressors in BC (CTNND1 23 , LIMA1 24 , AATF 25 ), and 4 has been identified as tumor suppressors in other cancer types (MEX3C 75 , UPF1 76 , CNOT1 77 , and TNKS1BP1 78 ). Interestingly, 5 have never been studied in cancer: CSTF2T, SRRM1, CPSF7, EIF4G3, and ELOA.…”

Section: Discussionmentioning

confidence: 99%

In silico analyses reveal new putative Breast Cancer RNA-binding proteins

Guerrero

López‐Cortés

García-Cárdenas

et al. 2020

Preprint

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Breast cancer (BC) is the leading cause of cancer-associated death among women worldwide. Despite treatment efforts, advanced BC with distant organ metastases is considered incurable. A better understanding of BC molecular processes is therefore of great interest to identify new therapeutic targets. Although large-scale efforts, such as The Cancer Genome Atlas (TCGA), have completely redefined cancer drug development, diagnosis, and treatment, additional key aspects of tumor biology remain to be discovered. In that respect, post-transcriptional regulation of tumorigenesis represents an understudied aspect of cancer research. As key regulators of this process, RNA-binding proteins (RBPs) are emerging as critical modulators of tumorigenesis but only few have defined roles in BC. To unravel new putative BC RBPs, we have performed in silico analyses of all human RBPs in three major cancer databases (TCGA-Breast Invasive Carcinoma, the Human Protein Atlas, and the Cancer Dependency Map project) along with complementary bioinformatics resources (STRING protein-protein interactions and the Network of Cancer Genes 6.0). Thus, we have identified six putative BC progressors (MRPL13, SCAMP3, CDC5L, DARS2, PUF60, and PLEC), and five BC suppressors RBPs (SUPT6H, MEX3C, UPF1, CNOT1, and TNKS1BP1). These proteins have never been studied in BC but show similar cancer-associated features than well-known BC proteins. Further research should focus on the mechanisms by which these proteins promote or suppress breast tumorigenesis, holding the promise of new therapeutic pathways along with novel drug development strategies.

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The CCR4-NOT complex is a tumor suppressor in Drosophila melanogaster eye cancer models

Cited by 15 publications

References 43 publications

Dual Repressive Function by Cip1, a Budding Yeast Analog of p21, in Cell-Cycle START Regulation

Dual Repressive Function by Cip1, a Budding Yeast Analog of p21, in Cell-Cycle START Regulation

Molecular characterization of the gibberellin-stimulated transcript of GASA4 in Citrus

In silico analyses reveal new putative Breast Cancer RNA-binding proteins

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