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PMID:23555679
| Citation |
Tang, MK, Liang, YJ, Chan, JY, Wong, SW, Chen, E, Yao, Y, Gan, J, Xiao, L, Leung, HC, Kung, HF, Wang, H and Lee, KK (2013) Promyelocytic Leukemia (PML) Protein Plays Important Roles in Regulating Cell Adhesion, Morphology, Proliferation and Migration. PLoS ONE 8:e59477 |
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| Abstract |
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. |
| Links |
PubMed PMC3605454 Online version:10.1371/journal.pone.0059477 |
| Keywords |
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| edit table |
Significance
Annotations
| Gene product | Qualifier | GO Term | Evidence Code | with/from | Aspect | Extension | Notes | Status |
|---|---|---|---|---|---|---|---|---|
| GO:0030155: regulation of cell adhesion |
ECO:0000315: |
P |
figure 3 |
complete | ||||
| GO:0010761: fibroblast migration |
ECO:0000315: |
P |
figure 5 |
complete | ||||
| GO:0048146: positive regulation of fibroblast proliferation |
ECO:0000315: |
P |
figure 4 |
complete | ||||
|
involved_in |
GO:0030155: regulation of cell adhesion |
ECO:0000315: mutant phenotype evidence used in manual assertion |
P |
Seeded From UniProt |
complete | |||
|
involved_in |
GO:0048146: positive regulation of fibroblast proliferation |
ECO:0000315: mutant phenotype evidence used in manual assertion |
P |
Seeded From UniProt |
complete | |||
|
involved_in |
GO:0010761: fibroblast migration |
ECO:0000315: mutant phenotype evidence used in manual assertion |
P |
Seeded From UniProt |
complete | |||
| GO:0008285: negative regulation of cell proliferation |
ECO:0000315: |
P |
figure 10 |
complete | ||||
|
involved_in |
GO:0008285: negative regulation of cell population proliferation |
ECO:0000315: mutant phenotype evidence used in manual assertion |
P |
Seeded From UniProt |
complete | |||
See also
References
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