Fetal Alz-50 clone 1 (FAC1) protein interacts with the Myc-associated zinc finger protein (ZF87/MAZ) and alters its transcriptional activity.
Transcription factors mediate their regulatory effects through interaction with DNA and numerous nuclear proteins. The fetal Alz-50 clone 1 (FAC1) protein, a novel DNA-binding protein with the capacity to repress transcription, is likely to function through a similar mechanism (1). Using the two-hybrid yeast screen, we have shown that FAC1 interacts with the myc-associated zinc finger protein (ZF87/MAZ). This association was confirmed in vitro with recombinant protein. The ZF87/MAZ interaction domain was mapped to the region containing a putative nuclear localization signal (NLS) and nuclear export sequence (NES) of FAC1, using deletion mutants of the FAC1 protein. FAC1, on the other hand, recognizes a conformational interface that includes the proline/alanine-rich domain of ZF87/MAZ and the first zinc finger. Cotransfection of NIH3T3 cells with ZF87/MAZ and a luciferase reporter containing the SV40 promoter and enhancer results in an increase in transcriptional activation, suggesting ZF87/MAZ is able to recognize its consensus binding site present in the SV40 promoter. Cotransfection with FAC1 reduces the level of ZF87/MAZ-induced activation of the SV40 promoter in a dose dependent manner. A mutant FAC1, lacking the ZF87/MAZ interaction domain, does not alter ZF87/MAZ activation of the SV40 promoter. These data demonstrate that interaction between FAC1 and ZF87/MAZ alters the transactivation capacity of ZF87/MAZ. By immunoblot analysis, FAC1 and ZF87/MAZ exhibit similar tissue distribution and co-localize to pathologic structures in Alzheimer's disease brain. Coexpression of FAC1 and ZF87/MAZ suggest that interaction of these two proteins will have biological implications for gene regulation in neurodegeneration.
Jordan-Sciutto
K L
KL
Departments of Pathology and Neurobiology, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA.
Dragich
J M
JM
Caltagarone
J
J
Hall
D J
DJ
Bowser
R
R
D016475:3T3 Cells; D000544:Alzheimer Disease / Q000378:metabolism; D000818:Animals; D034961:Antigens, Nuclear; D001692:Biological Transport; D004268:DNA-Binding Proteins; D006801:Humans; D015151:Immunoblotting; D051379:Mice; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D019913:Nuclear Localization Signals / Q000502:physiology; D009687:Nuclear Proteins / Q000378:metabolism; D009928:Organ Specificity; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism / Q000502:physiology; D014157:Transcription Factors / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D015533:Transcriptional Activation; D014162:Transfection; D016335:Zinc Fingers / Q000235:genetics; D000092468:Bromodomain Containing Proteins
D034961:Antigens, Nuclear; D004268:DNA-Binding Proteins; D009419:Nerve Tissue Proteins; D019913:Nuclear Localization Signals; D009687:Nuclear Proteins; D016271:Proto-Oncogene Proteins c-myc; D012097:Repressor Proteins; D014157:Transcription Factors; C076035:c-MYC-associated zinc finger protein; C406238:fetal Alzheimer antigen; D000092468:Bromodomain Containing Proteins