Translational control of cell growth and malignancy by the CPEBs

D’Ambrogio, Andrea; Nagaoka, Kentaro; Richter, Joel D.

doi:10.1038/nrc3485

Cited by 113 publications

(120 citation statements)

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“…CPEB3 is also regulated by miRNA. miR-107 is up-regulated and CPEB3 is down-regulated in HCC tissues compared with non-tumor tissues (6,20). In addition, miR-107 overexpression in the Huh7 and HepG2 HCC cells can down-regulate the CPEB3 expression by directly targeting the CPEB3 3'-UTR (6).…”

Section: Cpebs and Micrornamentioning

confidence: 88%

“…Proper balance between different isoforms of CPEBs is required to determine the cell fate between senescence and proliferation, while ectopic or unbalanced expression of the CPEB subtypes may contribute to tumor development (1,15,19). There is a report mentioning that CPEB1 is down-regulated in cancers of the reproductive system, CPEB 1-3 are down-regulated in brain cancers, CPEB3 and CPEB4 are down-regulated in cancers of the digestive system and CPEB4 is down-regulated in blood cell cancers (5); however, other reports showed contradictory results (1,15,19,20,22,23). Therefore, thorough understanding the characteristics of CPEBs it is important to clarify the role of various CPEBs in tumorigenesis and develop strategies for tumor therapy.…”

Section: Cpebs and Cancermentioning

confidence: 92%

“…These CPEBs direct coordinated programming of gene expression in the cells; however, anomalous expression of various CPEBs have been noted to be linked to the tumorigenesis, tumor growth, invasiveness and angiogenesis (1,15,19,20,22,23). Different CPEBs appear to play diverse roles in cancers.…”

Section: Resultsmentioning

confidence: 99%

“…CPEB1 levels are decreased in several types of human tumors, including ovary, stomach and breast cancers, myeloma, as well as colorectal and gastric cancer cell lines and myeloma cell lines (1,20,22,30,31). The reduced levels of CPEB1 have also been associated with the capacity of these malignant cells to promote invasion and angiogenesis (22,32).…”

Section: Cpeb1mentioning

confidence: 99%

“…CPEBs control cellular proliferation, chromosome segregation and cell differentiation; aberrant expression of CPEBs correlates with certain types of cancer, indicating that cytoplasmic RNA 3' end processing is important in the control of tumor cell growth (1,19,20). Several CPEBregulated mRNAs regulate cell-cycle progression, senescence and cell polarity (20). For example, the antiproliferative protein, Tob, a component of the Caf1-Ccr4 deadenylase complex, is involved in the regulation of the expression of the proto-oncogene myc (21).…”

Section: Cpebs and Cancermentioning

confidence: 99%

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Regulation of the Expression of Cytoplasmic Polyadenylation Element Binding Proteins for the Treatment of Cancer

Chen

Tsai

Tseng

2016

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Abstract. Regulated mRNA translation plays an important role in normal cellular functions and cytoplasmic polyadenylation element binding proteins (CPEBs) are the key factors that control the elongation of poly(A) tail during translation. The expression of various Translation and Cytoplasmic Polyadenylation Element Binding Proteins (CPEBs)Regulated mRNA translation plays an important role in normal cellular functions (1, 2). The translation of an mRNA is divided into three steps: initiation, elongation and termination (1). Among them, translation initiation is the rate-limiting, the most complex and the main target for translational control mechanisms (3). The 5'end of all transcribed mRNAs contains a 5'cap and the other end is blocked by a long stretch, usually in the order of 200-500 nucleotides of adenine residues (poly(A) tail) (1). Both the cap and the poly(A) tail of mRNAs act synergistically to facilitate translation (1). The translation is affected by a number of factors that stimulate or inhibit the translation of specific mRNAs (1, 2). Among these factors, RNAbinding proteins that recognize specific motifs in the 3' untranslated region (3'UTR) of their targets, are important (1, 2, 4). Of these RNA-binding proteins, cytoplasmic polyadenylation element binding protein (CPEB) family are sequence-specific RNA-binding proteins and the key factors controling the elongation of the poly(A) tail and polyadenylation-induced translation (2,5,6). CPEB binds the cytoplasmic polyadenylation element (CPE) in the 3' untranslated regions of responding mRNAs (2, 7-9). CPEB-mediated effects on translation require at least two CPEs separated by less than 50 nucleotides in the target mRNA, which indicates the formation of CPEB-dimer (10). CPEBs can recruit the translational repression or cytoplasmic polyadenylation machineries to their target mRNAs and nucleate a complex of factors that regulates poly(A) elongation through a deadenylating enzyme (1,4,7,(11)(12)(13). 5673

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Section: Cpebs and Micrornamentioning

confidence: 88%

Section: Cpebs and Cancermentioning

confidence: 92%

Section: Resultsmentioning

confidence: 99%

Section: Cpeb1mentioning

confidence: 99%

Section: Cpebs and Cancermentioning

confidence: 99%

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Regulation of the Expression of Cytoplasmic Polyadenylation Element Binding Proteins for the Treatment of Cancer

Chen

Tsai

Tseng

2016

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From Oocyte to Fertilizable Egg

Cragle

MacNicol

2014

Xenopus Development

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The primary point of regulation in control of messenger RNA (mRNA) translation occurs at initiation. Assembly of a functional ribosome onto an mRNA is a complex, multistep process. Two important regulated steps include the binding and formation of the 5′ cap complex, eIF4F, and recruitment of the small ribosomal subunit as part of a 43S preinitiation complex (Figure 3.1). Formation of both the cap complex and the preinitiation complex, specifically the ternary complex (the initiator methionine-charged tRNA i , the Abstract: Growing evidence indicates a critical role for posttranscriptional mechanisms for regulation of gene expression in a variety of developmental transitions as well as for control of adult somatic cell function. A predominant regulatory paradigm is selective control of messenger RNA (mRNA) translation. Significant advances have provided unparalleled insight into the diverse mRNA translational control processes that govern early development and cell cycle progression. At the forefront of these new insights is work analyzing oocyte maturation in the frog Xenopus laevis. We will review general concepts underlying mRNA translational regulation and highlight recent advances characterizing RNA binding proteins (RBP) and their target sequences in the control of oocyte growth and maturation. In particular, we will discuss the characterization of bifunctional elements, which can switch from repression to activation in response to changes in cellular signaling. We will consider the increasing number of mRNA 3′ untranslated regions (UTRs) containing multiple distinct elements with unique properties and the emerging issue of understanding the functional integration of translational control mechanisms. Finally, we will discuss the elucidation of nested feedback loops that drive and regulate sequential maternal mRNA translational control programs. These new advances indicate that regulated mRNA translation is likely to be much more complex than originally anticipated. The Xenopus oocyte is proving invaluable in the search for common underlying principles that guide mRNA translational control, that are applicable not only to oogenesis and maturation, but also to control of gene expression in somatic cells.

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Regulation of processing bodies: From viruses to cancer epigenetic machinery

Kanakamani

Suresh

Venkatesh

2020

Cell Biology International

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Processing bodies (PBs) are 100–300 nm cytoplasmic messenger ribonucleoprotein particle (mRNP) granules that regulate eukaryotic gene expression. These cytoplasmic compartments harbor messenger RNAs (mRNAs) and several proteins involved in mRNA decay, microRNA silencing, nonsense‐mediated mRNA decay, and splicing. Though membrane‐less, PB structures are maintained by RNA‐protein and protein‐protein interactions. PB proteins have intrinsically disordered regions and low complexity domains, which account for its liquid to liquid phase separation. In addition to being dynamic and actively involved in the exchange of materials with other mRNPs and organelles, they undergo changes on various cellular cues and environmental stresses, including viral infections. Interestingly, several PB proteins are individually implicated in cancer development, and no study has addressed the effects on PB dynamics after epigenetic modifications of cancer‐associated PB genes. In the current review, we summarize modulations undergone by P bodies or P body components upon viral infections. Furthermore, we discuss the selective and widely investigated PB proteins that undergo methylation changes in cancer and their potential as biomarkers.

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Translational control of cell growth and malignancy by the CPEBs

Cited by 113 publications

References 88 publications

Regulation of the Expression of Cytoplasmic Polyadenylation Element Binding Proteins for the Treatment of Cancer

Regulation of the Expression of Cytoplasmic Polyadenylation Element Binding Proteins for the Treatment of Cancer

From Oocyte to Fertilizable Egg

Regulation of processing bodies: From viruses to cancer epigenetic machinery

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