This title appears in the Scientific Report :
2014
Please use the identifier:
http://hdl.handle.net/2128/8221 in citations.
Analysis of the Bin1 SH3 interaction with peptides derived from the hepatitis C virus protein NS5A and c-Myc reveals that NS5A can competitively displace c-Myc in vitro
Analysis of the Bin1 SH3 interaction with peptides derived from the hepatitis C virus protein NS5A and c-Myc reveals that NS5A can competitively displace c-Myc in vitro
Severe liver damage like cirrhosis and hepatocellular carcinoma (HCC) can be caused by manifestation of the hepatitis C virus (HCV) infection. Constitutively activated c-Myc oncogene has been shown to contribute to the establishment of HCV-mediated HCC. Interestingly, only one of many isoforms of th...
Saved in:
Personal Name(s): | Aladag, Amine (Corresponding Author) |
---|---|
Bösing, Christina / Gremer, Lothar / Hoffmann, Silke / Klinker, Stefan / Schwarten, Melanie / Stoldt, Matthias / Valdau, Olga / Willbold, Dieter | |
Contributing Institute: |
Strukturbiochemie; ICS-6 |
Published in: | 2014 |
Imprint: |
2014
|
Conference: | 1st International Conference of Collaborative Research Center 974: Liver Damage and Regeneration, Düsseldorf (Germany), 2014-11-15 - 2014-11-16 |
Document Type: |
Proceedings |
Research Program: |
Structural Biology |
Link: |
Get full text OpenAccess |
Publikationsportal JuSER |
Severe liver damage like cirrhosis and hepatocellular carcinoma (HCC) can be caused by manifestation of the hepatitis C virus (HCV) infection. Constitutively activated c-Myc oncogene has been shown to contribute to the establishment of HCV-mediated HCC. Interestingly, only one of many isoforms of the tumor suppressor protein Bin1 (bridging integrator 1), Bin1+12A, contains an internal, canonical SH3 binding motif that recognizes its own SH3 domain. This leads to the inability of Bin1+12A to interact with c-Myc. The expression of the Bin1+12A isoform is a main phenotype in malignant melanoma cells. We suggest that also other mechanisms that disturb the interaction of Bin1 and c-Myc might have severe consequences since the latter is tightly regulated in healthy cells. The HCV nonstructural protein 5A (NS5A) plays a key role in virus replication and assembly. NS5A plays an intercepting role in several cellular pathways, which are linked to cell growth, cell cycle control, cell survival, cellular stress response, apoptosis as well as HCC. It is known that NS5A contains a highly conserved canonical, polyproline (PxxP) SH3-binding motif, which is located between its D2 and D3 domains. This PxxP motif was described to interact with the SH3 domain of Bin1. In addition to a biophysical analysis of the canonical binding between Bin1 SH3 and the PxxP motif of NS5A [1], we identified two additional low-affinity binding sites for non-canonical SH3 binding on NS5A [2]. The hypothesis underlying the work presented here is that viral NS5A is able to sequester cellular Bin1 from c-Myc. |