Interaction of Myc-associated zinc finger protein with DCC, the product of a tumor-suppressor gene, during the neural differentiation of P19 EC cells.
Expression of the DCC (deleted in colorectal cancer) protein is strongly induced during the neural differentiation of mouse P19 embryonal carcinoma (EC) cells that occurs when these cells are treated with retinoic acid (RA). Myc-associated zinc finger protein (MAZ) is a DNA-binding protein that is widely expressed and functions in human, mouse and hamster cells as an activator, an initiator or a terminator of transcription. However, the biological functions of MAZ remain elusive. We report here that MAZ associates with the cytoplasmic domain of the DCC protein in vivo and in vitro. Yeast two-hybrid assays confirmed this association. An immunofluorescence study demonstrated that DCC protein is expressed at elevated levels in neuron-like P19 EC cells, in particular in axons, in which the MAZ protein is also expressed. We found that MAZ was translocated from the nucleus to the cytoplasm during the RA-induced terminal differentiation of P19 EC cells with resultant loss of the ability of MAZ to bind to the ME1a1 site of the c-myc promoter. Taken together, our observations imply that the DCC protein might play a critical role as a signaling molecule in the regulation of the transcriptional activity of MAZ during the neural differentiation of P19 EC cells.
Ugai
H
H
Gene Engineering Division, Bioresource Center, Tsukuba Institute, RIKEN (The Institute of Physical and Chemical Research), 3-1-1 Koyadai, Tsukuba, Ibaraki, 305-0074, Japan.
Li
H O
HO
Komatsu
M
M
Tsutsui
H
H
Song
J
J
Shiga
T
T
Fearon
E
E
Murata
T
T
Yokoyama
K K
KK
D021581:Active Transport, Cell Nucleus; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D015152:Blotting, Northern; D015153:Blotting, Western; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002454:Cell Differentiation; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D000075389:DCC Receptor; D004268:DNA-Binding Proteins; D016259:Genes, myc / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism*; D010957:Plasmids / Q000378:metabolism; D011233:Precipitin Tests; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011956:Receptors, Cell Surface; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection; D014212:Tretinoin / Q000378:metabolism; D025521:Tumor Suppressor Proteins; D020798:Two-Hybrid System Techniques; D014981:Xenopus; D016335:Zinc Fingers
D015815:Cell Adhesion Molecules; D000075389:DCC Receptor; C501909:DCC protein, human; D004268:DNA-Binding Proteins; C501910:Dcc protein, mouse; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C076035:c-MYC-associated zinc finger protein; D014212:Tretinoin; D012313:RNA