title: Zac1 functional interactions mediate AP-1 transcriptional activity.
abstract: A zinc-finger protein which regulates apoptosis and cell cycle arrest 1 (Zac1) is a novel seven-zinc-finger protein that can bind a specific GC-rich DNA element and has intrinsic transactivation activity; therefore, its role as a transcription factor has been proposed. Zac1 not only promotes cell cycle arrest and apoptosis but also acts as a transcriptional cofactor for nuclear receptors and p53. In this study, we examined the functional roles of mouse Zac1 (mZac1) in HeLa cells treated with 12-O-tetradecanoylphorbol-13-acetate (PMA), a potent Activator protein 1 (AP-1) activator. At first, we found that mZac1 prolonged and enhanced PMA-induced AP-1 activity in both HeLa and HeLa/p53 shRNA cells. We further identified physical and functional interactions between mZac1 and AP-1 proteins (either c-Jun, c-Fos or both). Finally, we showed that Zac1 might function as a selective coactivator of AP-1, demonstrated by AP-1-dependent transcriptional activation of collagenase, c-Fos and p21(WAF1/Cip1) promoter activities. Identification of AP-1 as a specific target for Zac1-mediated transcriptional events not only establishes a direct link between these two pivotal regulatory proteins but also raises the possibility that Zac1 contributes to certain AP-1-dependent biological effects.
authors.affiliation: Department of Dermatology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC. ades0431@ms38.hinet.net
authors.forename: Wei-Ming
authors.initials: WM
authors.lastname: Wang
authors.forename: Shu-Ting
authors.initials: ST
authors.lastname: Liu
authors.forename: Shih-Ming
authors.initials: SM
authors.lastname: Huang
authors.forename: Wei-Shiang
authors.initials: WS
authors.lastname: Lin
authors.forename: Shyi-Gen
authors.initials: SG
authors.lastname: Chen
authors.forename: Yung-Lung
authors.initials: YL
authors.lastname: Chang
mesh_terms: D017209:Apoptosis; D015153:Blotting, Western; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006367:HeLa Cells; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics* / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D011401:Promoter Regions, Genetic; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C493956:CDKN1A protein, human; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; C106464:PLAGL1 protein, human; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C495901:TP53 protein, human; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D048031:JNK Mitogen-Activated Protein Kinases