Promyelocytic Leukemia PML Protein Plays Important Roles in Regulating Cell Adhesion, Morphology, Proliferation and MigrationReportar como inadecuado




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PML protein plays important roles in regulating cellular homeostasis. It forms PML nuclear bodies PML-NBs that act like nuclear relay stations and participate in many cellular functions. In this study, we have examined the proteome of mouse embryonic fibroblasts MEFs derived from normal PML+-+ and PML knockout PML−-− mice. The aim was to identify proteins that were differentially expressed when MEFs were incapable of producing PML. Using comparative proteomics, total protein were extracted from PML−-− and PML+-+ MEFs, resolved by two dimensional electrophoresis 2-DE gels and the differentially expressed proteins identified by LC-ESI-MS-MS. Nine proteins PML, NDRG1, CACYBP, CFL1, RSU1, TRIO, CTRO, ANXA4 and UBE2M were determined to be down-regulated in PML−-− MEFs. In contrast, ten proteins CIAPIN1, FAM50A, SUMO2 HSPB1 NSFL1C, PCBP2, YWHAG, STMN1, TPD52L2 and PDAP1 were found up-regulated. Many of these differentially expressed proteins play crucial roles in cell adhesion, migration, morphology and cytokinesis. The protein profiles explain why PML−-− and PML+-+ MEFs were morphologically different. In addition, we demonstrated PML−-− MEFs were less adhesive, proliferated more extensively and migrated significantly slower than PML+-+ MEFs. NDRG1, a protein that was down-regulated in PML−-− MEFs, was selected for further investigation. We determined that silencing NDRG1expression in PML+-+ MEFs increased cell proliferation and inhibited PML expression. Since NDRG expression was suppressed in PML−-− MEFs, this may explain why these cells proliferate more extensively than PML+-+ MEFs. Furthermore, silencing NDRG1expression also impaired TGF-β1 signaling by inhibiting SMAD3 phosphorylation.



Autor: Mei Kuen Tang , Yong Jia Liang, John Yeuk Hon Chan, Sing Wan Wong, Elve Chen, Yao Yao, Jingyi Gan, Lihai Xiao, Hin Cheung Leung,

Fuente: http://plos.srce.hr/



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