PMID:15701641

Citation	Jalota, A, Singh, K, Pavithra, L, Kaul-Ghanekar, R, Jameel, S and Chattopadhyay, S (2005) Tumor suppressor SMAR1 activates and stabilizes p53 through its arginine-serine-rich motif. J. Biol. Chem. 280:16019-29
Abstract	Various stresses and DNA-damaging agents trigger transcriptional activity of p53 by post-translational modifications, making it a global regulatory switch that controls cell proliferation and apoptosis. Earlier we have shown that the novel MAR-associated protein SMAR1 interacts with p53. Here we delineate the minimal domain of SMAR1 (the arginine-serine-rich domain) that is phosphorylated by protein kinase C family proteins and is responsible for p53 interaction, activation, and stabilization within the nucleus. SMAR1-mediated stabilization of p53 is brought about by inhibiting Mdm2-mediated degradation of p53. We also demonstrate that this arginine-serine (RS)-rich domain triggers the various cell cycle modulating proteins that decide cell fate. Furthermore, phenotypic knock-down experiments using small interfering RNA showed that SMAR1 is required for activation and nuclear retention of p53. The level of phosphorylated p53 was significantly increased in the thymus of SMAR1 transgenic mice, showing in vivo significance of SMAR1 expression. This is the first report that demonstrates the mechanism of action of the MAR-binding protein SMAR1 in modulating the activity of p53, often referred to as the "guardian of the genome."
Links	PubMed Online version:10.1074/jbc.M413200200
Keywords	Amino Acid Motifs; Animals; Arginine/genetics; Arginine/metabolism; Cell Cycle; Cell Cycle Proteins/genetics; Cell Cycle Proteins/metabolism; Cell Nucleus/metabolism; DNA-Binding Proteins/genetics; DNA-Binding Proteins/metabolism; Genes, Reporter; Mice; Mice, Transgenic; Microscopy, Confocal; Nuclear Proteins/genetics; Nuclear Proteins/metabolism; Phosphorylation; Proto-Oncogene Proteins/metabolism; Proto-Oncogene Proteins c-mdm2; Serine/genetics; Serine/metabolism; Thymus Gland/metabolism; Tumor Suppressor Protein p53/metabolism
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
MOUSE:BANP	enables	GO:0002039: p53 binding	ECO:0000314: direct assay evidence used in manual assertion		F		Seeded From UniProt	complete
MOUSE:BANP	part_of	GO:0005634: nucleus	ECO:0000314: direct assay evidence used in manual assertion		C		Seeded From UniProt	complete
MOUSE:BANP	acts_upstream_of_or_within	GO:0034504: protein localization to nucleus	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
MOUSE:BANP	acts_upstream_of_or_within	GO:0042177: negative regulation of protein catabolic process	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete

References

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