Fetal Alz-50 Clone 1 (FAC1) Protein Interacts with the Myc-Associated Zinc Finger Protein (ZF87/MAZ) and Alters Its Transcriptional Activity
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- 作者：K. L. Jordan-Sciutto ; J. M. Dragich ; J. Caltagarone ; D. J. Hall ; and R. Bowser
- 刊名：Biochemistry
- 出版年：2000
- 出版时间：March 28, 2000
- 年：2000
- 卷：39
- 期：12
- 页码：3206 - 3215
- 全文大小：442K
- 年卷期：v.39,no.12(March 28, 2000)
- ISSN：1520-4995
文摘
Transcription factors mediate their regulatory effects through interaction with DNA andnumerous nuclear proteins. The fetal Alz-50 clone 1 (FAC1) protein, a novel DNA-binding protein withthe capacity to repress transcription, is likely to function through a similar mechanism (1). Using thetwo-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 interactiondomain was mapped to the region containing a putative nuclear localization signal (NLS) and nuclearexport 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 andthe first zinc finger. Cotransfection of NIH3T3 cells with ZF87/MAZ and a luciferase reporter containingthe 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 withFAC1 reduces the level of ZF87/MAZ-induced activation of the SV40 promoter in a dose dependentmanner. A mutant FAC1, lacking the ZF87/MAZ interaction domain, does not alter ZF87/MAZ activationof the SV40 promoter. These data demonstrate that interaction between FAC1 and ZF87/MAZ alters thetransactivation capacity of ZF87/MAZ. By immunoblot analysis, FAC1 and ZF87/MAZ exhibit similartissue distribution and co-localize to pathologic structures in Alzheimer's disease brain. Coexpression ofFAC1 and ZF87/MAZ suggest that interaction of these two proteins will have biological implications forgene regulation in neurodegeneration.