SAFB1 interacts with and suppresses the transcriptional activity of p53.
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.
Department of Chemistry, Aristotle University of Thessaloniki, Thessaloniki, Greece.
Philippos
P
Peidis
Nikolaos
N
Voukkalis
Eleni
E
Aggelidou
Eleni
E
Georgatsou
Margarita
M
Hadzopoulou-Cladaras
Robert E
RE
Scott
Eleni
E
Nikolakaki
Thomas
T
Giannakouros
D000970:Antineoplastic Agents / Q000494:pharmacology; D002467:Cell Nucleus / Q000378:metabolism; D005472:Fluorouracil / Q000494:pharmacology; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D056945:Hep G2 Cells; D006801:Humans; D015151:Immunoblotting; D020014:K562 Cells; D036961:Matrix Attachment Region Binding Proteins / Q000235:genetics / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D034521:Nuclear Matrix-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D008926:Plicamycin / Q000494:pharmacology; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects; D034622:RNA Interference; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D020798:Two-Hybrid System Techniques
D000970:Antineoplastic Agents; D036961:Matrix Attachment Region Binding Proteins; D034521:Nuclear Matrix-Associated Proteins; D011960:Receptors, Estrogen; C109132:SAFB protein, human; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D049452:Green Fluorescent Proteins; C087728:SRPK1 protein, human; D017346:Protein Serine-Threonine Kinases; D008926:Plicamycin; D005472:Fluorouracil