| First Author | Luciano RL | Year | 2003 |
| Journal | J Biol Chem | Volume | 278 |
| Issue | 51 | Pages | 51116-24 |
| PubMed ID | 14532282 | Mgi Jnum | J:87274 |
| Mgi Id | MGI:2683995 | Doi | 10.1074/jbc.M303470200 |
| Citation | Luciano RL, et al. (2003) HCF-1 functions as a coactivator for the zinc finger protein Krox20. J Biol Chem 278(51):51116-24 |
| abstractText | HCF-1 is a transcriptional cofactor required for activation of herpes simplex virus immediate-early genes by VP16 as well as less clearly defined roles in cell proliferation, cytokinesis, and spliceosome formation. It is expressed as a large precursor that undergoes proteolysis to yield two subunits that remain stably associated. VP16 uses a degenerate 4-amino acid sequence, known as the HCF-binding motif, to bind to a six-bladed beta-propeller domain at the N terminus of HCF-1. Functional HCF-binding motifs are also found in LZIP and Zhangfei, two cellular bZIP transcription factors of unknown function. Here we show that the HCF-binding motif occurs in a wide spectrum of DNA-binding proteins and transcriptional cofactors. Three well characterized examples were further analyzed for their ability to use HCF-1 as a coactivator. Krox20, a zinc finger transcription factor required for Schwann cell differentiation, and E2F4, a cell cycle regulator, showed a strong requirement for functional HCF-1 to activate transcription. In contrast, activation by estrogen receptor-alpha did not display HCF dependence. In Krox20, the HCF-binding motif lies within the N-terminal activation domain and mutation of this sequence diminishes both transactivation and association with the HCF-1 beta-propeller. The activation domain in the C-terminal subunit of HCF-1 contributes to activation by Krox20, possibly through recruitment of p300. These results suggest that HCF-1 is recruited by many different classes of cellular transcription factors and is therefore likely to be required for a variety of cellular processes including cell cycle progression and development. |
