Analysis of MDM2 and MDM4 Single Nucleotide Polymorphisms, mRNA Splicing and Protein Expression in Retinoblastoma 英文参考文献.docVIP
- 1、本文档共11页,可阅读全部内容。
- 2、原创力文档(book118)网站文档一经付费(服务费),不意味着购买了该文档的版权,仅供个人/单位学习、研究之用,不得用于商业用途,未经授权,严禁复制、发行、汇编、翻译或者网络传播等,侵权必究。
- 3、本站所有内容均由合作方或网友上传,本站不对文档的完整性、权威性及其观点立场正确性做任何保证或承诺!文档内容仅供研究参考,付费前请自行鉴别。如您付费,意味着您自己接受本站规则且自行承担风险,本站不退款、不进行额外附加服务;查看《如何避免下载的几个坑》。如果您已付费下载过本站文档,您可以点击 这里二次下载。
- 4、如文档侵犯商业秘密、侵犯著作权、侵犯人身权等,请点击“版权申诉”(推荐),也可以打举报电话:400-050-0827(电话支持时间:9:00-18:30)。
- 5、该文档为VIP文档,如果想要下载,成为VIP会员后,下载免费。
- 6、成为VIP后,下载本文档将扣除1次下载权益。下载后,不支持退款、换文档。如有疑问请联系我们。
- 7、成为VIP后,您将拥有八大权益,权益包括:VIP文档下载权益、阅读免打扰、文档格式转换、高级专利检索、专属身份标志、高级客服、多端互通、版权登记。
- 8、VIP文档为合作方或网友上传,每下载1次, 网站将根据用户上传文档的质量评分、类型等,对文档贡献者给予高额补贴、流量扶持。如果你也想贡献VIP文档。上传文档
查看更多
Analysis of MDM2 and MDM4 Single Nucleotide Polymorphisms, mRNA Splicing and Protein Expression in Retinoblastoma 英文参考文献
AnalysisofMDM2andMDM4SingleNucleotide
Polymorphisms,mRNASplicingandProteinExpression
inRetinoblastoma
JustinaMcEvoy1,AnatolyUlyanov2,RachelBrennan1,GangWu2,StanleyPounds3,JinghuiZhang2,
MichaelA.Dyer1,4,5
*
1DepartmentofDevelopmentalNeurobiology,St.JudeChildren’sResearchHospital,Memphis,Tennessee,UnitedStatesofAmerica, 2DepartmentofComputational
Biology,St.JudeChildren’sResearchHospital,Memphis,Tennessee,UnitedStatesofAmerica,3DepartmentofStatistics,St.JudeChildren’sResearchHospital,Memphis,
Tennessee,UnitedStatesofAmerica,4DepartmentofOphthalmology,UniversityofTennesseeHealthScienceCenter,Memphis,Tennessee,UnitedStatesofAmerica,
5HowardHughesMedicalInstitute,ChevyChase,Maryland,UnitedStatesofAmerica
Abstract
Retinoblastomaisachildhoodcancerofthedevelopingretinathatbeginsinuteroandisdiagnosedinthefirstyearsoflife.
Biallelic RB1 gene inactivation is the initiating genetic lesion in retinoblastoma. The p53 gene is intact in human
retinoblastomabutthepathwayisbelievedtobesuppressedbyincreasedexpressionofMDM4(MDMX)andMDM2.Here
we quantify the expression of MDM4 and MDM2 mRNA and protein in human fetal retinae, primary retinoblastomas,
retinoblastomacelllinesandseveralindependentorthotopicretinoblastomaxenografts.WefoundthatMDM4isthemajor
p53antagonistexpressedinretinoblastomaandinthedevelopinghumanretina.WealsodiscoveredthatMDM4protein
steady state levels are much higher in retinoblastoma than in human fetal retinae. This increase would not have been
predictedbasedonthemRNAlevels.Weexploredseveralpossiblepost-transcriptionalmechanismsthatmaycontributeto
the elevated levels of MDM4 protein. A proportion of MDM4 transcripts are alternatively spliced to produce protein
products that are reported to be more stable and oncogenic. We also discovered that a microRNA predicted to target
MDM4(miR191)wasdownregulatedinretinoblastomarelativetohumanfetalretinaeandasubsetofsampleshadsomatic
mutations that eliminated the miR-191 binding site in the MDM4 mRNA. Taken together
您可能关注的文档
- An Unexpected Recurrent Transmission of Rift Valley Fever Virus in Cattle in a Temperate and Mountainous Area of Madagascar 英文参考文献.doc
- An Unbiased Assessment of the Role of Imprinted Genes in an Intergenerational Model of Developmental Programming 英文参考文献.doc
- An RNA Element at the 5′-End of the Poliovirus Genome Functions as a General Promoter for RNA Synthesis 英文参考文献.doc
- An Unusual Pterosaur Specimen (Pterodactyloidea, Azhdarchoidea) from the Early Cretaceous Romualdo Formation of Brazil, and the Evolution of the Pterodactyloid Palate 英文参考文献.doc
- An RNA Transport System in Candida albicans Regulates Hyphal Morphology and Invasive Growth 英文参考文献.doc
- An Unaccounted Fraction of Marine Biogenic CaCO3 Particles 英文参考文献.doc
- An Urgent Need to Restrict Access to Pesticides Based on Human Lethality 英文参考文献.doc
- An Unprecedented Role Reversal Ground Beetle Larvae (Coleoptera Carabidae) Lure Amphibians and Prey upon Them 英文参考文献.doc
- An Unmethylated 3′ Promoter-Proximal Region Is Required for Efficient Transcription Initiation 英文参考文献.doc
- An Unusual Helix Turn Helix Motif in the Catalytic Core of HIV-1 Integrase Binds Viral DNA and LEDGF 英文参考文献.doc
文档评论(0)