| First Author | Nakagawa K | Year | 2005 |
| Journal | Genes Cells | Volume | 10 |
| Issue | 8 | Pages | 835-50 |
| PubMed ID | 16098147 | Mgi Jnum | J:106849 |
| Mgi Id | MGI:3619676 | Doi | 10.1111/j.1365-2443.2005.00880.x |
| Citation | Nakagawa K, et al. (2005) Transcriptional activity of megakaryoblastic leukemia 1 (MKL1) is repressed by SUMO modification. Genes Cells 10(8):835-50 |
| abstractText | Megakaryoblastic leukemia 1 (MKL1) was originally identified as a gene translocated in megakaryoblastic leukemia. It has been shown that MKL1 functions as a RhoA-regulated transcriptional coactivator of serum response factor (SRF). In order to identify a protein that regulates the function of MKL1, we performed yeast two-hybrid screening and isolated cDNA that encodes UBC9, an E2 enzyme of small ubiquitin-related modifier-1 (SUMO-1), as an MKL1-binding protein. UBC9 was found to physically interact with MKL1 by GST pull-down assay, and MKL1 was covalently modified with SUMO-1 in 293T cells and in vitro reconstitution system. MKL1 sumoylation is enhanced by either serum stimulation or co-expression of constitutively active form of RhoA. Mutational analysis showed that lysine residues at 499, 576, and 624 are the major acceptor sites for SUMO-1. In addition, reporter gene analysis revealed that mutation of the three sumoylation sites strongly enhances the transcriptional activity of MKL1. The covalent attachment of SUMO-1 to MKL1 by gene fusion represses MKL1-dependent transcription in a complementary manner. Finally, mutation of the sumoylation sites of MKL1 also enhances SRF-dependent transcription without affecting MKL1-SRF interaction. The combined results demonstrated that MKL1 is sumoylated and this modification represses transcriptional activity of MKL1. |
