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Title: The MDM2-binding region in the transactivation domain of p53 also acts as a Bcl-XL-binding motif
Authors: Xu, Huibin
Ye, Hong
Osman, Nur Eliza
Sadler, Kristen
Won, Eun-Young
Chi, Seung-Wook
Yoon, Ho Sup
Keywords: DRNTU::Science::Biological sciences::Biochemistry
Issue Date: 2009
Source: 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.
Series/Report no.: Biochemistry
Abstract: 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.
DOI: 10.1021/bi901188s
Rights: © 2009 American Chemical Society.
Fulltext Permission: none
Fulltext Availability: No Fulltext
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