Tristetraprolin and E6-AP Killing the messenger in cervical cancer

University of South Carolina, Columbia, South Carolina, United States
Cell cycle (Georgetown, Tex.) (Impact Factor: 4.57). 08/2010; 9(16):3135-6. DOI: 10.4161/cc.9.16.12951
Source: PubMed


Comment on: Sanduja S, et al. Aging 2009;1:803-17.

Download full-text


Available from: Dan A Dixon, Mar 11, 2014
6 Reads
  • Source
    • "The minimal functional ARE sequence is a nonamer UUAUUUAWW [100]. Most RBPs binding to AREs promote rapid deadenylation and degradation of substrate mRNAs by targeting them to the exosome (e.g., TTP, AUF1, CUGBP2) [101]. On the contrary, HuR most often enhances the stability of its target mRNAs [3]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Posttranscriptional gene regulation is a rapid and efficient process to adjust the proteome of a cell to a changing environment. RNA-binding proteins (RBPs) are the master regulators of mRNA processing and translation and are often aberrantly expressed in cancer. In addition to well-studied transcription factors, RBPs are emerging as fundamental players in tumor development. RBPs and their mRNA targets form a complex network that plays a crucial role in tumorigenesis. This paper describes mechanisms by which RBPs influence the expression of well-known oncogenes, focusing on precise examples that illustrate the versatility of RBPs in posttranscriptional control of cancer development. RBPs appeared very early in evolution, and new RNA-binding domains and combinations of them were generated in more complex organisms. The identification of RBPs, their mRNA targets, and their mechanism of action have provided novel potential targets for cancer therapy.
    Comparative and Functional Genomics 05/2012; 2012(3):178525. DOI:10.1155/2012/178525 · 2.03 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Integrated high-risk human papillomavirus (HPV) DNA was frequently detected in the genomes of cervical carcinoma cells. The HPV E6 and E7 oncoproteins disrupt the functions of tumor suppressors p53 and Rb; thus, understanding the mechanism by which HPV E6 and E7 gene expression is regulated in cancer cells is highly relevant to cancer biology. Brg1 is a catalytic subunit of the SWI/SNF chromatin remodeling complexes that function in the transcriptional regulation of certain cellular genes. Here, we show that knockdown of Brg1 in HeLa cells leads to cell cycle arrest, p53 and Rb protein accumulation and, interestingly, downregulated expression of HPV18 E6 and E7 genes. Brg1 binds the HPV18 LCR in a JunB- and p300-dependent manner and is required for efficient recruitment of RNA polymerase II to the HPV18 LCR. The function of Brg1 in HPV18 gene regulation is unique given that its homolog Brm does not play a role in this regulatory pathway, and this may help design target-specific intervention strategies.
    Cell cycle (Georgetown, Tex.) 02/2012; 11(3):617-27. DOI:10.4161/cc.11.3.19115 · 4.57 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The role of inflammation in skeletal muscle adaptation to exercise is complex and has hardly been elucidated so far. While the acute inflammatory response to exercise seems to promote skeletal muscle training adaptation and regeneration, persistent, low-grade inflammation, as seen in a multitude of chronic diseases, is obviously detrimental. The regulation of cytokine production in skeletal muscle cells has been relatively well studied, yet little is known about the compensatory and anti-inflammatory mechanisms that resolve inflammation and restore tissue homeostasis. One important strategy to ensure sequential, timely and controlled resolution of inflammation relies on the regulated stability of mRNAs encoding pro-inflammatory mediators. Many key transcripts in early immune responses are characterized by the presence of AU-rich elements (AREs) in the 3'-untranslated regions of their mRNAs, allowing efficient fine-tuning of gene expression patterns at the post-transcriptional level. AREs exert their function by recruiting particular RNA-binding proteins, resulting, in most cases, in de-stabilization of the target transcripts. The best-characterized ARE-binding proteins are HuR, CUGBP1, KSRP, AUF1, and the three ZFP36 proteins, especially TTP/ZFP36. Here, we give a general introduction into the role of inflammation in the adaptation of skeletal muscle to exercise. Subsequently, we focus on potential roles of ARE-binding proteins in skeletal muscle tissue in general and specifically exercise-induced skeletal muscle remodeling. Finally, we present novel data suggesting a specific function of TTP/ZFP36 in exercise-induced skeletal muscle plasticity.
    Exercise immunology review 04/2015; 21:42-57. · 4.18 Impact Factor