Promyelocytic Leukemia (PML) Protein Plays Important Roles in Regulating Cell Adhesion, Morphology, Proliferation and Migration

Autor: Lihai Xiao, Sing Wan Wong, Kenneth Ka Ho Lee, John Yeuk-Hon Chan, Hin Cheung Leung, Jingyi Gan, Mei Kuen Tang, Yao Yao, Hua Wang, Hsiang-Fu Kung, Yong Jia Liang, Elve Chen
Rok vydání: 2013
Předmět:
Proteomics
Proteome
viruses
Cellular homeostasis
Cell Cycle Proteins
Promyelocytic Leukemia Protein
Biochemistry
Mice
Cell Movement
Molecular Cell Biology
Signaling in Cellular Processes
Nuclear protein
Spectrometric Identification of Proteins
Multidisciplinary
biology
Physics
Chemotaxis
Intracellular Signaling Peptides and Proteins
Nuclear Proteins
virus diseases
Cellular Structures
Extracellular Matrix
Cell biology
Cell Motility
embryonic structures
Cytochemistry
Medicine
Signal transduction
Research Article
Signal Transduction
Science
Biophysics
Cell Growth
Transforming Growth Factor beta1
Promyelocytic leukemia protein
Cell Adhesion
otorhinolaryngologic diseases
Animals
Gene Silencing
Cell adhesion
Biology
Extracellular Matrix Adhesions
Cell Proliferation
Cell growth
Tumor Suppressor Proteins
Proteins
Fibroblasts
biochemical phenomena
metabolism
and nutrition
Molecular biology
Subcellular Organelles
Gene Expression Regulation
Membrane protein
biology.protein
Gene Deletion
Cytokinesis
Transcription Factors
Zdroj: PLoS ONE
PLoS ONE, Vol 8, Iss 3, p e59477 (2013)
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0059477
Popis: 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.
Databáze: OpenAIRE
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