p53 Family: Role of Protein Isoforms in Human Cancer

Department of Surgery and Cancer Biology, Vanderbilt University Medical Center, 1255 Light Hall, 2215 Garland Avenue, Nashville, TN 37232, USA.
Journal of nucleic acids 01/2012; 2012(2090-0201):687359. DOI: 10.1155/2012/687359
Source: PubMed


TP53, TP63, and TP73 genes comprise the p53 family. Each gene produces protein isoforms through multiple mechanisms including extensive alternative mRNA splicing. Accumulating evidence shows that these isoforms play a critical role in the regulation of many biological processes in normal cells. Their abnormal expression contributes to tumorigenesis and has a profound effect on tumor response to curative therapy. This paper is an overview of isoform diversity in the p53 family and its role in cancer.

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Available from: Jinxiong Wei, Jun 30, 2014
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    • "For instance, the human tumor-suppressor TP53 gene produces 12 different isoforms through AS, alternative initiation of translation and promoter usage. Although they are expressed in normal human tissues, the balance between these isoforms is altered in a wide range of cancer types contributing to tumorigenesis and to the response to therapy [25]. Thus, deciphering the circuits that control AS of TP53 transcripts may assist in the development of personalized therapies. "
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    ABSTRACT: Alternative splicing emerges as a potent and pervasive mechanism of gene expression regulation that expands the coding capacity of the genome and forms an intermediate layer of regulation between transcriptional and post-translational networks. Indeed, alternative splicing occupies a pivotal position in developmental programs and in the cell response to external and internal stimuli. Not surprisingly, therefore, its deregulation frequently leads to human disease. In this review we provide an updated overview of the impact of alternative splicing on tumorigenesis. Moreover, we discuss the intricacy of the reciprocal interactions between alternative splicing programs and signal transduction pathways, which appear to be crucially linked to cancer progression in response to the tumor microenvironment. Finally we focus on the recently described interplay between splicing and chromatin organization which is expected to shed new lights into gene expression regulation in normal and cancer cells.
    Seminars in Cell and Developmental Biology 08/2014; 32. DOI:10.1016/j.semcdb.2014.03.016 · 6.27 Impact Factor
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    • "P53 plays a vital role in carcinogenesis, and many studies have revealed that it is involved with MDR (22). In addition to regulation of apoptosis, P53 modulates the expression of P-gp. "
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    ABSTRACT: Overexpression of cytokine-induced apoptosis inhibitor 1 (CIAPIN1) contributes to multidrug resistance (MDR) in breast cancer. This study aimed to evaluate the potential of CIAPIN1 gene silencing by RNA interference (RNAi) as a treatment for drug-resistant breast cancer and to investigate the effect of CIAPIN1 on the drug resistance of breast cancer in vivo. We used lentivirus-vector-based RNAi to knock down CIAPIN1 in nude mice bearing MDR breast cancer tumors and found that lentivirus-vector-mediated silencing of CIAPIN1 could efficiently and significantly inhibit tumor growth when combined with chemotherapy in vivo. Furthermore, Western blot analysis showed that both CIAPIN1 and P-glycoprotein expression were efficiently downregulated, and P53 was upregulated, after RNAi. Therefore, we concluded that lentivirus-vector-mediated RNAi targeting of CIAPIN1 is a potential approach to reverse MDR of breast cancer. In addition, CIAPIN1 may participate in MDR of breast cancer by regulating P-glycoprotein and P53 expression.
    Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas / Sociedade Brasileira de Biofisica ... [et al.] 03/2014; DOI:10.1590/1414-431X20133356 · 1.01 Impact Factor
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    • "The p53 is a transcription factor which prevents free radical-induced gene mutations by detecting and getting rid of oxidatively damaged DNA [76]. Upon stimulation, p53 also induces a host of other genes which in turn cause cell cycle arrest and apoptosis [76, 77]. The loss of function of p53 family is known to contribute to cancer progression. "
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    ABSTRACT: Cancer cells generate reactive oxygen species (ROS) resulting from mitochondrial dysfunction, stimulation of oncogenes, abnormal metabolism, and aggravated inflammatory activities. Available evidence also suggests that cancer cells depend on intrinsic ROS level for proliferation and survival. Both physiological and pathophysiological roles have been ascribed to ROS which cause lipid peroxidation. In spite of their injurious effects, the ROS and the resulting lipid peroxidation products could be beneficial in cancer treatment. This review presents research findings suggesting that ROS and the resulting lipid peroxidation products could be utilized to inhibit cancer growth or induce cancer cell death. It also underscores the potential of lipid peroxidation products to potentiate the antitumor effect of other anticancer agents. The review also highlights evidence demonstrating other potential applications of lipid peroxidation products in cancer treatment. These include the prospect of lipid peroxidation products as a diagnostic tool to predict the chances of cancer recurrence, to monitor treatment progress or how well cancer patients respond to therapy. Further and detailed research is required on how best to successfully, effectively, and selectively target cancer cells in humans using lipid peroxidation products. This may prove to be an important strategy to complement current treatment regimens for cancer patients.
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