DC Field | Value | Language |
---|---|---|
dc.contributor.author | Mi-Kyung Yoon | - |
dc.contributor.author | B Y Kim | - |
dc.contributor.author | J Y Lee | - |
dc.contributor.author | Ji-Hyang Ha | - |
dc.contributor.author | Sung Ah Kim | - |
dc.contributor.author | Dong-Hwa Lee | - |
dc.contributor.author | Min-Sung Lee | - |
dc.contributor.author | Mi-Kyung Lee | - |
dc.contributor.author | Jin Sun Choi | - |
dc.contributor.author | Jin Hwa Cho | - |
dc.contributor.author | Jeong Hoon Kim | - |
dc.contributor.author | Sunhong Kim | - |
dc.contributor.author | J Song | - |
dc.contributor.author | Sung Goo Park | - |
dc.contributor.author | Byoung Chul Park | - |
dc.contributor.author | Kwang-Hee Bae | - |
dc.contributor.author | S U Choi | - |
dc.contributor.author | Seung-Wook Chi | - |
dc.date.accessioned | 2019-01-23T16:30:55Z | - |
dc.date.available | 2019-01-23T16:30:55Z | - |
dc.date.issued | 2018 | - |
dc.identifier.issn | 0021-9258 | - |
dc.identifier.uri | 10.1074/jbc.RA118.003061 | ko |
dc.identifier.uri | https://oak.kribb.re.kr/handle/201005/18241 | - |
dc.description.abstract | In response to genotoxic stress, the tumor suppressor protein p73 induces apoptosis and cell cycle arrest. Despite extensive studies on p73-mediated apoptosis, little is known about the cytoplasmic apoptotic function of p73. Here, using H1299 lung cancer cells and diverse biochemical approaches, including colony formation, DNA fragmentation, GST pulldown, and apoptosis assays along with NMR spectroscopy, we show that p73 induces transcription-independent apoptosis via its transactivation domain (TAD) through a mitochondrial pathway and that this apoptosis is mediated by the interaction between p73-TAD and the anti-apoptotic protein B-cell lymphoma-extra large (Bcl-XL or BCL2L1). This binding disrupted an interaction between Bcl-XL and the pro-apoptotic protein BH3-interacting domain death agonist (Bid). In particular, we found that a 16-mer p73-TAD peptide motif (p73-TAD16) mediates transcription-independent apoptosis, accompanied by cytochrome c release from the mitochondria, by interacting with Bcl-XL Interestingly, the structure of the Bcl-XL-p73-TAD16 peptide complex revealed a novel mechanism of Bcl-XL recognition by p73-TAD. We observed that the α-helical p73-TAD16 peptide binds to a noncanonical site in Bcl-XL, comprising the BH1, BH2, and BH3 domains in an orientation opposite to those of pro-apoptotic BH3 peptides. Taken together, our results indicate that the cytoplasmic apoptotic function of p73 is mediated through a noncanonical mode of Bcl-XL recognition. This finding sheds light on a critical transcription-independent, p73-mediated mechanism for apoptosis induction, which has potential implications for anticancer therapy. | - |
dc.publisher | Amer Soc Biochemistry Molecular Biology Inc | - |
dc.title | Cytoplasmic pro-apoptotic function of the tumor suppressor p73 is mediated through a modified mode of recognition of the anti-apoptotic regulator Bcl-XL | - |
dc.title.alternative | Cytoplasmic pro-apoptotic function of the tumor suppressor p73 is mediated through a modified mode of recognition of the anti-apoptotic regulator Bcl-XL | - |
dc.type | Article | - |
dc.citation.title | Journal of Biological Chemistry | - |
dc.citation.number | 51 | - |
dc.citation.endPage | 19558 | - |
dc.citation.startPage | 19546 | - |
dc.citation.volume | 293 | - |
dc.contributor.affiliatedAuthor | Mi-Kyung Yoon | - |
dc.contributor.affiliatedAuthor | Ji-Hyang Ha | - |
dc.contributor.affiliatedAuthor | Sung Ah Kim | - |
dc.contributor.affiliatedAuthor | Dong-Hwa Lee | - |
dc.contributor.affiliatedAuthor | Min-Sung Lee | - |
dc.contributor.affiliatedAuthor | Mi-Kyung Lee | - |
dc.contributor.affiliatedAuthor | Jin Sun Choi | - |
dc.contributor.affiliatedAuthor | Jin Hwa Cho | - |
dc.contributor.affiliatedAuthor | Jeong Hoon Kim | - |
dc.contributor.affiliatedAuthor | Sunhong Kim | - |
dc.contributor.affiliatedAuthor | Sung Goo Park | - |
dc.contributor.affiliatedAuthor | Byoung Chul Park | - |
dc.contributor.affiliatedAuthor | Kwang-Hee Bae | - |
dc.contributor.affiliatedAuthor | Seung-Wook Chi | - |
dc.contributor.alternativeName | 윤미경 | - |
dc.contributor.alternativeName | 김부연 | - |
dc.contributor.alternativeName | 이지영 | - |
dc.contributor.alternativeName | 하지향 | - |
dc.contributor.alternativeName | 김성아 | - |
dc.contributor.alternativeName | 이동화 | - |
dc.contributor.alternativeName | 이민성 | - |
dc.contributor.alternativeName | 이미경 | - |
dc.contributor.alternativeName | 최진선 | - |
dc.contributor.alternativeName | 조진화 | - |
dc.contributor.alternativeName | 김정훈 | - |
dc.contributor.alternativeName | 김선홍 | - |
dc.contributor.alternativeName | 송재환 | - |
dc.contributor.alternativeName | 박성구 | - |
dc.contributor.alternativeName | 박병철 | - |
dc.contributor.alternativeName | 배광희 | - |
dc.contributor.alternativeName | 최상운 | - |
dc.contributor.alternativeName | 지승욱 | - |
dc.identifier.bibliographicCitation | Journal of Biological Chemistry, vol. 293, no. 51, pp. 19546-19558 | - |
dc.identifier.doi | 10.1074/jbc.RA118.003061 | - |
dc.description.journalClass | Y | - |
There are no files associated with this item.
Items in OpenAccess@KRIBB are protected by copyright, with all rights reserved, unless otherwise indicated.