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RASSF Signalling and DNA Damage: Monitoring the Integrity of the Genome? RASSF信号传导和DNA损伤:监测基因组的完整性?
Molecular biology international Pub Date : 2012-01-01 Epub Date: 2012-04-11 DOI: 10.1155/2012/141732
Simon F Scrace, Eric O'Neill
{"title":"RASSF Signalling and DNA Damage: Monitoring the Integrity of the Genome?","authors":"Simon F Scrace,&nbsp;Eric O'Neill","doi":"10.1155/2012/141732","DOIUrl":"https://doi.org/10.1155/2012/141732","url":null,"abstract":"<p><p>The RASSF family of proteins has been extensively studied in terms of their genetics, structure and function. One of the functions that has been increasingly studied is the role of the RASSF proteins in the DNA damage response. Surprisingly, this research, which encompasses both the classical and N-terminal RASSF proteins, has revealed an involvement of the RASSFs in oncogenic pathways as well as the more familiar tumour suppressor pathways usually associated with the RASSF family members. The most studied protein with respect to DNA damage is RASSF1A, which has been shown, not only to be activated by ATM, a major regulator of the DNA damage response, but also to bind to and activate a number of different pathways which all lead to and feedback from the guardian of the genome, p53. In this review we discuss the latest research linking the RASSF proteins to DNA damage signalling and maintenance of genomic integrity and look at how this knowledge is being utilised in the clinic to enhance the effectiveness of traditional cancer therapies such as radiotherapy.</p>","PeriodicalId":74217,"journal":{"name":"Molecular biology international","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/141732","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30611965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 19
Loss of RASSF2 Enhances Tumorigencity of Lung Cancer Cells and Confers Resistance to Chemotherapy. RASSF2的缺失增强肺癌细胞的致瘤性并赋予化疗耐药性。
Molecular biology international Pub Date : 2012-01-01 Epub Date: 2012-05-24 DOI: 10.1155/2012/705948
Jennifer Clark, Jessica Freeman, Howard Donninger
{"title":"Loss of RASSF2 Enhances Tumorigencity of Lung Cancer Cells and Confers Resistance to Chemotherapy.","authors":"Jennifer Clark,&nbsp;Jessica Freeman,&nbsp;Howard Donninger","doi":"10.1155/2012/705948","DOIUrl":"https://doi.org/10.1155/2012/705948","url":null,"abstract":"<p><p>RASSF2 is a novel pro-apoptotic effector of K-Ras that is frequently inactivated in a variety of primary tumors by promoter methylation. Inactivation of RASSF2 enhances K-Ras-mediated transformation and overexpression of RASSF2 suppresses tumor cell growth. In this study, we confirm that RASSF2 and K-Ras form an endogenous complex, validating that RASSF2 is a bona fide K-Ras effector. We adopted an RNAi approach to determine the effects of inactivation of RASSF2 on the transformed phenotype of lung cancer cells containing an oncogenic K-Ras. Loss of RASSF2 expression resulted in a more aggressive phenotype that was characterized by enhanced cell proliferation and invasion, decreased cell adhesion, the ability to grow in an anchorage-independent manner and cell morphological changes. This enhanced transformed phenotype of the cells correlated with increased levels of activated AKT, indicating that RASSF2 can modulate Ras signaling pathways. Loss of RASSF2 expression also confers resistance to taxol and cisplatin, two frontline therapeutics for the treatment of lung cancer. Thus we have shown that inactivation of RASSF2, a process that occurs frequently in primary tumors, enhances the transforming potential of activated K-Ras and our data suggests that RASSF2 may be a novel candidate for epigenetic-based therapy in lung cancer.</p>","PeriodicalId":74217,"journal":{"name":"Molecular biology international","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/705948","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30687451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 20
Mechanisms of HIV Transcriptional Regulation and Their Contribution to Latency. HIV转录调控机制及其对潜伏期的影响。
Molecular biology international Pub Date : 2012-01-01 Epub Date: 2012-06-03 DOI: 10.1155/2012/614120
Gillian M Schiralli Lester, Andrew J Henderson
{"title":"Mechanisms of HIV Transcriptional Regulation and Their Contribution to Latency.","authors":"Gillian M Schiralli Lester,&nbsp;Andrew J Henderson","doi":"10.1155/2012/614120","DOIUrl":"https://doi.org/10.1155/2012/614120","url":null,"abstract":"<p><p>Long-lived latent HIV-infected cells lead to the rebound of virus replication following antiretroviral treatment interruption and present a major barrier to eliminating HIV infection. These latent reservoirs, which include quiescent memory T cells and tissue-resident macrophages, represent a subset of cells with decreased or inactive proviral transcription. HIV proviral transcription is regulated at multiple levels including transcription initiation, polymerase recruitment, transcription elongation, and chromatin organization. How these biochemical processes are coordinated and their potential role in repressing HIV transcription along with establishing and maintaining latency are reviewed.</p>","PeriodicalId":74217,"journal":{"name":"Molecular biology international","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/614120","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30693086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 59
TRIM22: A Diverse and Dynamic Antiviral Protein. TRIM22:一种多样的动态抗病毒蛋白。
Molecular biology international Pub Date : 2012-01-01 Epub Date: 2012-05-08 DOI: 10.1155/2012/153415
Clayton J Hattlmann, Jenna N Kelly, Stephen D Barr
{"title":"TRIM22: A Diverse and Dynamic Antiviral Protein.","authors":"Clayton J Hattlmann,&nbsp;Jenna N Kelly,&nbsp;Stephen D Barr","doi":"10.1155/2012/153415","DOIUrl":"https://doi.org/10.1155/2012/153415","url":null,"abstract":"The tripartite motif (TRIM) family of proteins is an evolutionarily ancient group of proteins with homologues identified in both invertebrate and vertebrate species. Human TRIM22 is one such protein that has a dynamic evolutionary history that includes gene expansion, gene loss, and strong signatures of positive selection. To date, TRIM22 has been shown to restrict the replication of a number of viruses, including encephalomyocarditis virus (EMCV), hepatitis B virus (HBV), and human immunodeficiency virus type 1 (HIV-1). In addition, TRIM22 has also been implicated in cellular differentiation and proliferation and may play a role in certain cancers and autoimmune diseases. This comprehensive paper summarizes our current understanding of TRIM22 structure and function.","PeriodicalId":74217,"journal":{"name":"Molecular biology international","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/153415","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30657823","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 51
RASSF1A Signaling in the Heart: Novel Functions beyond Tumor Suppression. 心脏中的RASSF1A信号:肿瘤抑制之外的新功能
Molecular biology international Pub Date : 2012-01-01 Epub Date: 2012-04-10 DOI: 10.1155/2012/154283
Dominic P Del Re, Junichi Sadoshima
{"title":"RASSF1A Signaling in the Heart: Novel Functions beyond Tumor Suppression.","authors":"Dominic P Del Re,&nbsp;Junichi Sadoshima","doi":"10.1155/2012/154283","DOIUrl":"https://doi.org/10.1155/2012/154283","url":null,"abstract":"<p><p>The RASSF proteins are a family of polypeptides, each containing a conserved Ras association domain, suggesting that these scaffold proteins may be effectors of activated Ras or Ras-related small GTPases. RASSF proteins are characterized by their ability to inhibit cell growth and proliferation while promoting cell death. RASSF1 isoform A is an established tumor suppressor and is frequently silenced in a variety of tumors and human cancer cell lines. However, our understanding of its function in terminally differentiated cell types, such as cardiac myocytes, is relatively nascent. Herein, we review the role of RASSF1A in cardiac physiology and disease and highlight signaling pathways that mediate its function.</p>","PeriodicalId":74217,"journal":{"name":"Molecular biology international","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/154283","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30611964","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 10
HIV-1 Reverse Transcriptase Still Remains a New Drug Target: Structure, Function, Classical Inhibitors, and New Inhibitors with Innovative Mechanisms of Actions. HIV-1逆转录酶仍然是一个新的药物靶点:结构、功能、经典抑制剂和具有创新作用机制的新抑制剂
Molecular biology international Pub Date : 2012-01-01 Epub Date: 2012-06-20 DOI: 10.1155/2012/586401
Francesca Esposito, Angela Corona, Enzo Tramontano
{"title":"HIV-1 Reverse Transcriptase Still Remains a New Drug Target: Structure, Function, Classical Inhibitors, and New Inhibitors with Innovative Mechanisms of Actions.","authors":"Francesca Esposito,&nbsp;Angela Corona,&nbsp;Enzo Tramontano","doi":"10.1155/2012/586401","DOIUrl":"https://doi.org/10.1155/2012/586401","url":null,"abstract":"<p><p>During the retrotranscription process, characteristic of all retroviruses, the viral ssRNA genome is converted into integration-competent dsDNA. This process is accomplished by the virus-coded reverse transcriptase (RT) protein, which is a primary target in the current treatments for HIV-1 infection. In particular, in the approved therapeutic regimens two classes of drugs target RT, namely, nucleoside RT inhibitors (NRTIs) and nonnucleoside RT inhibitors (NNRTIs). Both classes inhibit the RT-associated polymerase activity: the NRTIs compete with the natural dNTP substrate and act as chain terminators, while the NNRTIs bind to an allosteric pocket and inhibit polymerization noncompetitively. In addition to these two classes, other RT inhibitors (RTIs) that target RT by distinct mechanisms have been identified and are currently under development. These include translocation-defective RTIs, delayed chain terminators RTIs, lethal mutagenesis RTIs, dinucleotide tetraphosphates, nucleotide-competing RTIs, pyrophosphate analogs, RT-associated RNase H function inhibitors, and dual activities inhibitors. This paper describes the HIV-1 RT function and molecular structure, illustrates the currently approved RTIs, and focuses on the mechanisms of action of the newer classes of RTIs.</p>","PeriodicalId":74217,"journal":{"name":"Molecular biology international","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/586401","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30750611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 94
Förster Resonance Energy Transfer between Core/Shell Quantum Dots and Bacteriorhodopsin. 核/壳量子点与细菌发光素之间的福斯特共振能量转移
Molecular biology international Pub Date : 2012-01-01 Epub Date: 2012-06-10 DOI: 10.1155/2012/910707
Mark H Griep, Eric M Winder, Donald R Lueking, Gregory A Garrett, Shashi P Karna, Craig R Friedrich
{"title":"Förster Resonance Energy Transfer between Core/Shell Quantum Dots and Bacteriorhodopsin.","authors":"Mark H Griep, Eric M Winder, Donald R Lueking, Gregory A Garrett, Shashi P Karna, Craig R Friedrich","doi":"10.1155/2012/910707","DOIUrl":"10.1155/2012/910707","url":null,"abstract":"<p><p>An energy transfer relationship between core-shell CdSe/ZnS quantum dots (QDs) and the optical protein bacteriorhodopsin (bR) is shown, demonstrating a distance-dependent energy transfer with 88.2% and 51.1% of the QD energy being transferred to the bR monomer at separation distances of 3.5 nm and 8.5 nm, respectively. Fluorescence lifetime measurements isolate nonradiative energy transfer, other than optical absorptive mechanisms, with the effective QD excited state lifetime reducing from 18.0 ns to 13.3 ns with bR integration, demonstrating the Förster resonance energy transfer contributes to 26.1% of the transferred QD energy at the 3.5 nm separation distance. The established direct energy transfer mechanism holds the potential to enhance the bR spectral range and sensitivity of energies that the protein can utilize, increasing its subsequent photocurrent generation, a significant potential expansion of the applicability of bR in solar cell, biosensing, biocomputing, optoelectronic, and imaging technologies.</p>","PeriodicalId":74217,"journal":{"name":"Molecular biology international","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3376779/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30720445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Prevention of lysosomal storage diseases and derivation of mutant stem cell lines by preimplantation genetic diagnosis. 通过植入前遗传学诊断预防溶酶体贮积病和突变干细胞系的衍生。
Molecular biology international Pub Date : 2012-01-01 Epub Date: 2012-12-26 DOI: 10.1155/2012/797342
Gheona Altarescu, Rachel Beeri, Rachel Eiges, Silvina Epsztejn-Litman, Talia Eldar-Geva, Deborah Elstein, Ari Zimran, Ehud J Margalioth, Ephrat Levy-Lahad, Paul Renbaum
{"title":"Prevention of lysosomal storage diseases and derivation of mutant stem cell lines by preimplantation genetic diagnosis.","authors":"Gheona Altarescu,&nbsp;Rachel Beeri,&nbsp;Rachel Eiges,&nbsp;Silvina Epsztejn-Litman,&nbsp;Talia Eldar-Geva,&nbsp;Deborah Elstein,&nbsp;Ari Zimran,&nbsp;Ehud J Margalioth,&nbsp;Ephrat Levy-Lahad,&nbsp;Paul Renbaum","doi":"10.1155/2012/797342","DOIUrl":"https://doi.org/10.1155/2012/797342","url":null,"abstract":"<p><p>Preimplantation genetic diagnosis (PGD) allows birth of unaffected children for couples at risk for a genetic disorder. We present the strategy and outcome of PGD for four lysosomal storage disorders (LSD): Tay-Sachs disease (TSD), Gaucher disease (GD), Fabry disease (FD), and Hunter syndrome (HS), and subsequent development of stem cell lines. For each disease, we developed a family-specific fluorescent multiplex single-cell PCR protocol that included the familial mutation and informative markers surrounding the mutation. Embryo biopsy and PGD analysis were performed on either oocytes (polar bodies one and two) or on single blastomeres from a six-cell embryo. We treated twenty families carrying mutations in these lysosomal storage disorders, including 3 couples requiring simultaneous analysis for two disorders (TSD/GD, TSD/balanced Robertsonian translocation 45XYder(21;14), and HS/oculocutaneus albinism). These analyses led to an overall pregnancy rate/embryo transfer of 38% and the birth of 20 unaffected children from 17 families. We have found that PGD for lysosomal disorders is a safe and effective method to prevent birth of affected children. In addition, by using mutant embryos for the derivation of stem cell lines, we have successfully established GD and HS hESC lines for use as valuable models in LSD research.</p>","PeriodicalId":74217,"journal":{"name":"Molecular biology international","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/797342","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31162942","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 13
APOBEC3 versus Retroviruses, Immunity versus Invasion: Clash of the Titans. APOBEC3与逆转录病毒,免疫与入侵:泰坦之战。
Molecular biology international Pub Date : 2012-01-01 Epub Date: 2012-06-06 DOI: 10.1155/2012/974924
Ann M Sheehy, Julie Erthal
{"title":"APOBEC3 versus Retroviruses, Immunity versus Invasion: Clash of the Titans.","authors":"Ann M Sheehy,&nbsp;Julie Erthal","doi":"10.1155/2012/974924","DOIUrl":"https://doi.org/10.1155/2012/974924","url":null,"abstract":"<p><p>Since the identification of APOBEC3G (A3G) as a potent restriction factor of HIV-1, a tremendous amount of effort has led to a broadened understanding of both A3G and the APOBEC3 (A3) family to which it belongs. In spite of the fine-tuned viral counterattack to A3 activity, in the form of the HIV-1 Vif protein, enthusiasm for leveraging the Vif : A3G axis as a point of clinical intervention remains high. In an impressive explosion of information over the last decade, additional A3 family members have been identified as antiviral proteins, mechanistic details of the restrictive capacity of these proteins have been elucidated, structure-function studies have revealed important molecular details of the Vif : A3G interaction, and clinical cohorts have been scrutinized for correlations between A3 expression and function and viral pathogenesis. In the last year, novel and unexpected findings regarding the role of A3G in immunity have refocused efforts on exploring the potential of harnessing the natural power of this immune defense. These most recent reports allude to functions of the A3 proteins that extend beyond their well-characterized designation as restriction factors. The emerging story implicates the A3 family as not only defense proteins, but also as participants in the broader innate immune response.</p>","PeriodicalId":74217,"journal":{"name":"Molecular biology international","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/974924","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30708295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 14
Dynamic Association between HIV-1 Gag and Membrane Domains. HIV-1 Gag 与膜域间的动态关联
Molecular biology international Pub Date : 2012-01-01 Epub Date: 2012-07-05 DOI: 10.1155/2012/979765
Ian B Hogue, G Nicholas Llewellyn, Akira Ono
{"title":"Dynamic Association between HIV-1 Gag and Membrane Domains.","authors":"Ian B Hogue, G Nicholas Llewellyn, Akira Ono","doi":"10.1155/2012/979765","DOIUrl":"10.1155/2012/979765","url":null,"abstract":"<p><p>HIV-1 particle assembly is driven by the structural protein Gag. Gag binds to and multimerizes on the inner leaflet of the plasma membrane, eventually resulting in formation of spherical particles. During virus spread among T cells, Gag accumulates to the plasma membrane domain that, together with target cell membrane, forms a cell junction known as the virological synapse. While Gag association with plasma membrane microdomains has been implicated in virus assembly and cell-to-cell transmission, recent studies suggest that, rather than merely accumulating to pre-existing microdomains, Gag plays an active role in reorganizing the microdomains via its multimerization activity. In this paper, we will discuss this emerging view of Gag microdomain interactions. Relationships between Gag multimerization and microdomain association will be further discussed in the context of Gag localization to T-cell uropods and virological synapses.</p>","PeriodicalId":74217,"journal":{"name":"Molecular biology international","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3399408/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30787577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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