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PMID:23555679

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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

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


Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:PML

GO:0030155: regulation of cell adhesion

ECO:0000315:

P

figure 3

complete
CACAO 7525

MOUSE:PML

GO:0010761: fibroblast migration

ECO:0000315:

P

figure 5

complete
CACAO 7527

MOUSE:PML

GO:0048146: positive regulation of fibroblast proliferation

ECO:0000315:

P

figure 4

complete
CACAO 7526

MOUSE:PML

involved_in

GO:0030155: regulation of cell adhesion

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:PML

involved_in

GO:0048146: positive regulation of fibroblast proliferation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:PML

involved_in

GO:0010761: fibroblast migration

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:NDRG1

GO:0008285: negative regulation of cell proliferation

ECO:0000315:

P

figure 10

complete
CACAO 7676

MOUSE:NDRG1

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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