| First Author | Kasahara H | Year | 2001 |
| Journal | J Biol Chem | Volume | 276 |
| Issue | 7 | Pages | 4570-80 |
| PubMed ID | 11042197 | Mgi Jnum | J:148078 |
| Mgi Id | MGI:3843444 | Doi | 10.1074/jbc.M004995200 |
| Citation | Kasahara H, et al. (2001) Characterization of homo- and heterodimerization of cardiac Csx/Nkx2.5 homeoprotein. J Biol Chem 276(7):4570-80 |
| abstractText | Csx/Nkx2.5 is an evolutionarily conserved homeodomain (HD)-containing transcription factor that is essential for early cardiac development. We found that the HD of Csx/Nkx2.5 binds as a monomer as well as a dimer to its DNA binding sites in the promoter of the atrial natriuretic factor (ANF) gene, an in vivo target gene of Csx/Nkx2.5. Csx/Nkx2.5 physically interacts with each other in vitro as well as in cells, and the HD is critical for homodimerization. Lys(193) and Arg(194), located at the COOH-terminal end of HD, are essential for dimerization. Lys(193) is also required for a specific interaction with the zinc finger transcription factor GATA4. Csx/Nkx2.5 can heterodimerize with other NK2 homeodomain proteins, Nkx2.3 and Nkx2.6/Tix, with different affinities. A single missense mutation, Ile(183) to Pro in the HD of Csx/Nkx2.5, preserved homodimerization function, but totally abolished DNA binding. Ile(183) --> Pro mutant acts in an inhibitory manner on wild type Csx/Nkx2.5 transcriptional activity through the ANF promoter in 10T1/2 cells. However, Ile(183) --> Pro mutant does not inhibit wild type Csx/Nkx2.5 function on the ANF promoter in cultured neonatal cardiac myocytes, possibly due to failure of dimerization in the presence of the target DNA. These results suggest that complex protein-protein interactions of Csx/Nkx2.5 play a role in its transcriptional regulatory function. |
