Abstract
A significant amount of nuclear p53 is found associated with the nuclear matrix in cells that were exposed to genotoxic stress. In this study we identified Scaffold attachment factor B1 (SAFB1), a nuclear matrix-associated protein that binds the scaffold or matrix attachment regions (S/MARs) of genomic DNA, as a novel p53-interacting protein. SAFB1 was able to associate with p53 through its C-terminal domain, while significant co-localization of the two proteins was observed in cells treated with 5-fluorouracil or mithramycin. Binding of p53 to SAFB1 had a significant functional outcome, since SAFB1 was shown to suppress p53-mediated reporter gene expression. These data suggest that nuclear matrix-associated proteins may play a critical role in regulating p53 localization and activity.
Copyright © 2010 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Antineoplastic Agents / pharmacology
-
Cell Nucleus / metabolism
-
Fluorouracil / pharmacology
-
Green Fluorescent Proteins / genetics
-
Green Fluorescent Proteins / metabolism
-
HEK293 Cells
-
Hep G2 Cells
-
Humans
-
Immunoblotting
-
K562 Cells
-
Matrix Attachment Region Binding Proteins / genetics
-
Matrix Attachment Region Binding Proteins / metabolism*
-
Microscopy, Fluorescence
-
Nuclear Matrix-Associated Proteins / genetics
-
Nuclear Matrix-Associated Proteins / metabolism*
-
Plicamycin / pharmacology
-
Protein Binding
-
Protein Serine-Threonine Kinases / genetics
-
Protein Serine-Threonine Kinases / metabolism
-
Protein Transport / drug effects
-
RNA Interference
-
Receptors, Estrogen / genetics
-
Receptors, Estrogen / metabolism*
-
Transcriptional Activation*
-
Transfection
-
Tumor Suppressor Protein p53 / genetics
-
Tumor Suppressor Protein p53 / metabolism*
-
Two-Hybrid System Techniques
Substances
-
Antineoplastic Agents
-
Matrix Attachment Region Binding Proteins
-
Nuclear Matrix-Associated Proteins
-
Receptors, Estrogen
-
SAFB protein, human
-
TP53 protein, human
-
Tumor Suppressor Protein p53
-
Green Fluorescent Proteins
-
SRPK1 protein, human
-
Protein Serine-Threonine Kinases
-
Plicamycin
-
Fluorouracil