Biophysical characterization and modeling of human Ecdysoneless (ECD) protein supports a scaffolding function
| Autor: | Paul L. Sorgen, Nicholas P. Schafer, Hamid Band, Jeffrey J. Lovelace, Gaelle Spagnol, Vimla Band, Gloria E. O. Borgstahl, Peter D. Simone, Riyaz A. Mir, Admir Kellezi, Carol Kolar |
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| Rok vydání: | 2016 |
| Předmět: |
Scaffold protein
genetic structures Biophysics Biochemistry Article 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation Structural Biology Ecdysoneless E2F lcsh:QH301-705.5 Molecular Biology Transcription factor 030304 developmental biology R2TP complex 0303 health sciences molecular modeling Chemistry SAXS Cell cycle circular dichroism structural hub Cell biology lcsh:Biology (General) scaffold protein 030220 oncology & carcinogenesis Phosphorylation P53 binding |
| Zdroj: | AIMS Biophysics, Vol 3, Iss 1, Pp 195-210 (2016) AIMS biophysics |
| ISSN: | 2377-9098 |
| DOI: | 10.3934/biophy.2016.1.195 |
| Popis: | The human homolog of Drosophila ecdysoneless protein (ECD) is a p53 binding protein that stabilizes and enhances p53 functions. Homozygous deletion of mouse Ecd is early embryonic lethal and Ecd deletion delays G1-S cell cycle progression. Importantly, ECD directly interacts with the Rb tumor suppressor and competes with the E2F transcription factor for binding to Rb. Further studies demonstrated ECD is overexpressed in breast and pancreatic cancers and its overexpression correlates with poor patient survival. ECD overexpression together with Ras induces cellular transformation through upregulation of autophagy. Recently we demonstrated that CK2 mediated phosphorylation of ECD and interaction with R2TP complex are important for its cell cycle regulatory function. Considering that ECD is a component of multiprotein complexes and its crystal structure is unknown, we characterized ECD structure by circular dichroism measurements and sequence analysis software. These analyses suggest that the majority of ECD is composed of α-helices. Furthermore, small angle X-ray scattering (SAXS) analysis showed that deletion fragments, ECD(1–432) and ECD(1–534), are both well-folded and reveals that the first 400 residues are globular and the next 100 residues are in an extended cylindrical structure. Taking all these results together, we speculate that ECD acts like a structural hub or scaffolding protein in its association with its protein partners. In the future, the hypothetical model presented here for ECD will need to be tested experimentally. |
| Databáze: | OpenAIRE |
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