Translational Control of Cell Growth and Malignancy by the CPEBs

Overview

Journal Nat Rev Cancer

Specialty Oncology

Date 2013 Mar 1

PMID 23446545

Citations 71

Authors

Andrea DAmbrogio

Kentaro Nagaoka

Joel D Richter

Affiliations

Soon will be listed here.

Abstract

The cytoplasmic polyadenylation element binding proteins (CPEBs) associate with specific sequences in mRNA 3' untranslated regions to promote translation. They do so by inducing cytoplasmic polyadenylation, which requires specialized poly(A) polymerases. Aberrant expression of these proteins correlates with certain types of cancer, indicating that cytoplasmic RNA 3' end processing is important in the control of growth. Several CPEB-regulated mRNAs govern cell cycle progression, regulate senescence, establish cell polarity, and promote tumorigenesis and metastasis. In this Opinion article, we discuss the emerging evidence that indicates a key role for the CPEBs in cancer biology.

Citing Articles

Cytoplasmic regulation of the poly(A) tail length as a potential therapeutic target.

Fernandez M, Mendez R RNA. 2025; 31(3):402-415.

PMID: 39805658 PMC: 11874964. DOI: 10.1261/rna.080333.124.

Prognostic insights, immune infiltration, and therapeutic response: Cytoplasmic poly(A) tail regulators in hepatocellular carcinoma.

Liu Y, Huang Y, Le Y, Gao Y, Wang H, Yang J Mol Ther Oncol. 2024; 32(2):200816.

PMID: 38948919 PMC: 11214399. DOI: 10.1016/j.omton.2024.200816.

CPEB1 Controls NRF2 Proteostasis and Ferroptosis Susceptibility in Pancreatic Cancer.

Zhang S, Huang J, Lan Z, Xiao Y, Liao Y, Basnet S Int J Biol Sci. 2024; 20(8):3156-3172.

PMID: 38904009 PMC: 11186365. DOI: 10.7150/ijbs.95962.

circKDM1A suppresses bladder cancer progression by sponging miR-889-3p/CPEB3 and stabilizing p53 mRNA.

Chen H, Wen J, Zhang W, Ma W, Guo Y, Shen L iScience. 2024; 27(4):109624.

PMID: 38632984 PMC: 11022052. DOI: 10.1016/j.isci.2024.109624.

TOB1 and TOB2 mark distinct RNA processing granules in differentiating lens fiber cells.

Perez R, Yang X, Familari M, Martinez G, Lovicu F, Hime G J Mol Histol. 2024; 55(1):121-138.

PMID: 38165569 DOI: 10.1007/s10735-023-10177-y.

References

Jing H, Kase J, Dorr J, Milanovic M, Lenze D, Grau M . Opposing roles of NF-κB in anti-cancer treatment outcome unveiled by cross-species investigations. Genes Dev. 2011; 25(20):2137-46. PMC: 3205584. DOI: 10.1101/gad.17620611. View

Kadyk L, Kimble J . Genetic regulation of entry into meiosis in Caenorhabditis elegans. Development. 1998; 125(10):1803-13. DOI: 10.1242/dev.125.10.1803. View

Ortiz-Zapater E, Pineda D, Martinez-Bosch N, Fernandez-Miranda G, Iglesias M, Alameda F . Key contribution of CPEB4-mediated translational control to cancer progression. Nat Med. 2011; 18(1):83-90. DOI: 10.1038/nm.2540. View

Collado M, Blasco M, Serrano M . Cellular senescence in cancer and aging. Cell. 2007; 130(2):223-33. DOI: 10.1016/j.cell.2007.07.003. View

Sonenberg N . Translation factors as effectors of cell growth and tumorigenesis. Curr Opin Cell Biol. 1993; 5(6):955-60. DOI: 10.1016/0955-0674(93)90076-3. View

Novoa I, Gallego J, Ferreira P, Mendez R . Mitotic cell-cycle progression is regulated by CPEB1 and CPEB4-dependent translational control. Nat Cell Biol. 2010; 12(5):447-56. DOI: 10.1038/ncb2046. View

Thomson J, Newman M, Parker J, Morin-Kensicki E, Wright T, Hammond S . Extensive post-transcriptional regulation of microRNAs and its implications for cancer. Genes Dev. 2006; 20(16):2202-7. PMC: 1553203. DOI: 10.1101/gad.1444406. View

McGrew L, Richter J . Translational control by cytoplasmic polyadenylation during Xenopus oocyte maturation: characterization of cis and trans elements and regulation by cyclin/MPF. EMBO J. 1990; 9(11):3743-51. PMC: 552130. DOI: 10.1002/j.1460-2075.1990.tb07587.x. View

DAmbrogio A, Gu W, Udagawa T, Mello C, Richter J . Specific miRNA stabilization by Gld2-catalyzed monoadenylation. Cell Rep. 2012; 2(6):1537-45. PMC: 3534910. DOI: 10.1016/j.celrep.2012.10.023. View

10.

Sarkissian M, Mendez R, Richter J . Progesterone and insulin stimulation of CPEB-dependent polyadenylation is regulated by Aurora A and glycogen synthase kinase-3. Genes Dev. 2004; 18(1):48-61. PMC: 314275. DOI: 10.1101/gad.1136004. View

11.

Shamji A, Nghiem P, Schreiber S . Integration of growth factor and nutrient signaling: implications for cancer biology. Mol Cell. 2003; 12(2):271-80. DOI: 10.1016/j.molcel.2003.08.016. View

12.

Katoh T, Sakaguchi Y, Miyauchi K, Suzuki T, Kashiwabara S, Baba T . Selective stabilization of mammalian microRNAs by 3' adenylation mediated by the cytoplasmic poly(A) polymerase GLD-2. Genes Dev. 2009; 23(4):433-8. PMC: 2648654. DOI: 10.1101/gad.1761509. View

13.

Wu L, Wells D, Tay J, Mendis D, Abbott M, Barnitt A . CPEB-mediated cytoplasmic polyadenylation and the regulation of experience-dependent translation of alpha-CaMKII mRNA at synapses. Neuron. 1998; 21(5):1129-39. DOI: 10.1016/s0896-6273(00)80630-3. View

14.

Kuge H, Richter J . Cytoplasmic 3' poly(A) addition induces 5' cap ribose methylation: implications for translational control of maternal mRNA. EMBO J. 1995; 14(24):6301-10. PMC: 394754. DOI: 10.1002/j.1460-2075.1995.tb00320.x. View

15.

Tay J, Richter J . Germ cell differentiation and synaptonemal complex formation are disrupted in CPEB knockout mice. Dev Cell. 2001; 1(2):201-13. DOI: 10.1016/s1534-5807(01)00025-9. View

16.

Kalluri R, Weinberg R . The basics of epithelial-mesenchymal transition. J Clin Invest. 2009; 119(6):1420-8. PMC: 2689101. DOI: 10.1172/JCI39104. View

17.

Jung M, Lorenz L, Richter J . Translational control by neuroguidin, a eukaryotic initiation factor 4E and CPEB binding protein. Mol Cell Biol. 2006; 26(11):4277-87. PMC: 1489097. DOI: 10.1128/MCB.02470-05. View

18.

Michaloglou C, Vredeveld L, Soengas M, Denoyelle C, Kuilman T, van der Horst C . BRAFE600-associated senescence-like cell cycle arrest of human naevi. Nature. 2005; 436(7051):720-4. DOI: 10.1038/nature03890. View

19.

Pavlopoulos E, Trifilieff P, Chevaleyre V, Fioriti L, Zairis S, Pagano A . Neuralized1 activates CPEB3: a function for nonproteolytic ubiquitin in synaptic plasticity and memory storage. Cell. 2011; 147(6):1369-83. PMC: 3442370. DOI: 10.1016/j.cell.2011.09.056. View

20.

Ingolia N, Brar G, Rouskin S, McGeachy A, Weissman J . The ribosome profiling strategy for monitoring translation in vivo by deep sequencing of ribosome-protected mRNA fragments. Nat Protoc. 2012; 7(8):1534-50. PMC: 3535016. DOI: 10.1038/nprot.2012.086. View