p67 isoform of mouse disabled 2 protein acts as a transcriptional activator during the differentiation of F9 cells.
The mouse disabled 2 (mDab2) gene is a mouse homologue of the Drosophila disabled gene and is alternatively spliced to form two isoforms, p96 and p67. Although p96 has been known to regulate the Ras-Sos G-protein signal transduction pathway by interacting with Grb2, little is known about the biological function of p67. Recent studies have shown that the expression of mDab2 is markedly up-regulated during the retinoic acid (RA)-induced differentiation of F9 cells, suggesting another role for mDab2 in cell differentiation [Cho, Lee and Park (1999) Mol. Cells 9, 179-184). In the present study, we first elucidated the biological function of p67 isoform of mDab2 and identified its binding partner. Unlike p96, p67 largely resides in RA-treated F9 cell nuclei. In this system, p67 interacts with mouse androgen-receptor interacting protein 3, termed the mDab2 interacting protein, which acts as a transcriptional co-regulator. By using a fusion protein with a heterologous DNA-binding domain (GAL4), we showed that p67 had an intrinsic transcriptional activation function. These results suggest that mDab2 p67 may function as a transcriptional co-factor for certain complexes of transcriptional regulatory elements involved in the RA-induced differentiation of F9 cells.
Cho
S Y
SY
Graduate School of Biotechnology, Korea University, 1, 5-ka, Anam-dong, Sungbuk-ku, Seoul 136-701, Korea.
Jeon
J W
JW
Lee
S H
SH
Park
S S
SS
D016475:3T3 Cells; D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D000818:Animals; D051017:Apoptosis Regulatory Proteins; D001665:Binding Sites; D019556:COS Cells; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D002467:Cell Nucleus / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D004268:DNA-Binding Proteins; D016147:Genes, Tumor Suppressor; D051379:Mice; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009687:Nuclear Proteins / Q000737:chemistry; D010750:Phosphoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011233:Precipitin Tests; D011485:Protein Binding; D050828:Protein Inhibitors of Activated STAT; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011506:Proteins; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D015534:Trans-Activators / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D014162:Transfection; D014212:Tretinoin / Q000494:pharmacology; D025521:Tumor Suppressor Proteins; D020798:Two-Hybrid System Techniques; D044767:Ubiquitin-Protein Ligases
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D051017:Apoptosis Regulatory Proteins; C102885:DAB2 protein, human; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; D050828:Protein Inhibitors of Activated STAT; D020033:Protein Isoforms; D011506:Proteins; D011993:Recombinant Fusion Proteins; D015534:Trans-Activators; D025521:Tumor Suppressor Proteins; D014212:Tretinoin; C485521:Miz1 protein, mouse; D044767:Ubiquitin-Protein Ligases; C484534:Pias2 protein, rat