The MDM2-binding region in the transactivation domain of p53 also acts as a Bcl-XL-binding motif
While the transcription-dependent mechanism of p53 has been extensively studied, recently the transcription-independent apoptotic activity of p53 has also been described. Bcl-2 and Bcl-XL interact with p53 and induce apoptosis. Initially, the p53 DNA-binding domain (p53DBD) was found to bind to Bcl-...
| Main Authors: | , , , , , , |
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| Format: | Journal Article |
| Language: | English |
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2012
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| Online Access: | https://hdl.handle.net/10356/93855 http://hdl.handle.net/10220/7476 |
| _version_ | 1826111509223178240 |
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| author | Xu, Huibin Ye, Hong Osman, Nur Eliza Sadler, Kristen Won, Eun-Young Chi, Seung-Wook Yoon, Ho Sup |
| author2 | School of Biological Sciences |
| author_facet | School of Biological Sciences Xu, Huibin Ye, Hong Osman, Nur Eliza Sadler, Kristen Won, Eun-Young Chi, Seung-Wook Yoon, Ho Sup |
| author_sort | Xu, Huibin |
| collection | NTU |
| description | While the transcription-dependent mechanism of p53 has been extensively studied, recently the transcription-independent apoptotic activity of p53 has also been described. Bcl-2 and Bcl-XL interact with p53 and induce apoptosis. Initially, the p53 DNA-binding domain (p53DBD) was found to bind to Bcl-2 and Bcl-XL. Later, the p53 N-terminal domain (p53NTD) was reported to be sufficient for inducing the transcription-independent apoptotic activity of p53 and also shown to interact with Bcl-XL. Here, we further document that the transactivation domain of p53 (p53TAD) in p53NTD alone binds to Bcl-XL. We demonstrated that the MDM2-binding region (residues S15 to N29, herein referred to as SN15) in p53TAD is the binding site for Bcl-XL. The binding interface on Bcl-XL was identified at the hydrophobic pocket formed by the BH1, BH2, and BH3 domains, which also binds to the Bak/Bad BH3 peptides, suggesting Bcl-XL and MDM2 share a common binding motif in p53TAD. Our NMR structural studies have shown that the SN15 peptide undergoes a conformational change upon binding to Bcl-XL. A Bcl-XL/SN15 complex structural model suggests that the SN15 peptide adopts an extended α-helical structure to bind to the hydrophobic pocket on the Bcl-XL, which is similar to the mode of binding between BH3 peptides and Bcl-XL. |
| first_indexed | 2024-10-01T02:51:54Z |
| format | Journal Article |
| id | ntu-10356/93855 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T02:51:54Z |
| publishDate | 2012 |
| record_format | dspace |
| spelling | ntu-10356/938552020-03-07T12:18:12Z The MDM2-binding region in the transactivation domain of p53 also acts as a Bcl-XL-binding motif Xu, Huibin Ye, Hong Osman, Nur Eliza Sadler, Kristen Won, Eun-Young Chi, Seung-Wook Yoon, Ho Sup School of Biological Sciences DRNTU::Science::Biological sciences::Biochemistry While the transcription-dependent mechanism of p53 has been extensively studied, recently the transcription-independent apoptotic activity of p53 has also been described. Bcl-2 and Bcl-XL interact with p53 and induce apoptosis. Initially, the p53 DNA-binding domain (p53DBD) was found to bind to Bcl-2 and Bcl-XL. Later, the p53 N-terminal domain (p53NTD) was reported to be sufficient for inducing the transcription-independent apoptotic activity of p53 and also shown to interact with Bcl-XL. Here, we further document that the transactivation domain of p53 (p53TAD) in p53NTD alone binds to Bcl-XL. We demonstrated that the MDM2-binding region (residues S15 to N29, herein referred to as SN15) in p53TAD is the binding site for Bcl-XL. The binding interface on Bcl-XL was identified at the hydrophobic pocket formed by the BH1, BH2, and BH3 domains, which also binds to the Bak/Bad BH3 peptides, suggesting Bcl-XL and MDM2 share a common binding motif in p53TAD. Our NMR structural studies have shown that the SN15 peptide undergoes a conformational change upon binding to Bcl-XL. A Bcl-XL/SN15 complex structural model suggests that the SN15 peptide adopts an extended α-helical structure to bind to the hydrophobic pocket on the Bcl-XL, which is similar to the mode of binding between BH3 peptides and Bcl-XL. 2012-01-26T01:28:28Z 2019-12-06T18:46:41Z 2012-01-26T01:28:28Z 2019-12-06T18:46:41Z 2009 2009 Journal Article Xu, H., Ye, H., Osman, N. E., Sadler, K., Won, E. -Y., Chi, S. -W., et al. (2009). The MDM2-Binding Region in the Transactivation Domain of p53 Also Acts as a Bcl-XL-Binding Motif, Biochemistry, 48(51), 12159-12168. https://hdl.handle.net/10356/93855 http://hdl.handle.net/10220/7476 10.1021/bi901188s en Biochemistry © 2009 American Chemical Society. |
| spellingShingle | DRNTU::Science::Biological sciences::Biochemistry Xu, Huibin Ye, Hong Osman, Nur Eliza Sadler, Kristen Won, Eun-Young Chi, Seung-Wook Yoon, Ho Sup The MDM2-binding region in the transactivation domain of p53 also acts as a Bcl-XL-binding motif |
| title | The MDM2-binding region in the transactivation domain of p53 also acts as a Bcl-XL-binding motif |
| title_full | The MDM2-binding region in the transactivation domain of p53 also acts as a Bcl-XL-binding motif |
| title_fullStr | The MDM2-binding region in the transactivation domain of p53 also acts as a Bcl-XL-binding motif |
| title_full_unstemmed | The MDM2-binding region in the transactivation domain of p53 also acts as a Bcl-XL-binding motif |
| title_short | The MDM2-binding region in the transactivation domain of p53 also acts as a Bcl-XL-binding motif |
| title_sort | mdm2 binding region in the transactivation domain of p53 also acts as a bcl xl binding motif |
| topic | DRNTU::Science::Biological sciences::Biochemistry |
| url | https://hdl.handle.net/10356/93855 http://hdl.handle.net/10220/7476 |
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