[1]Junling Zhang,Xiaolei Xue,Qinghui Meng,等.RBAP96 Mediates Radiosensitivity of Breast Cancer Cells via Interacting with Retinoblastoma Protein[J].国际放射医学核医学杂志,2016,40(5):323-328.[doi:10.3760/cma.j.issn.1673-4114.2016.05.001]
　Junling Zhang,Xiaolei Xue,Qinghui Meng,et al.RBAP96 Mediates Radiosensitivity of Breast Cancer Cells via Interacting with Retinoblastoma Protein[J].International Journal of Radiation Medicine and Nuclear Medicine,2016,40(5):323-328.[doi:10.3760/cma.j.issn.1673-4114.2016.05.001]
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RBAP96 Mediates Radiosensitivity of Breast Cancer Cells via Interacting with Retinoblastoma Protein(/HTML)
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《国际放射医学核医学杂志》[ISSN:1673-4114/CN:12-1381/R]

卷:
40
期数:
2016年第5期
页码:
323-328
栏目:
论著
出版日期:
2016-09-25

文章信息/Info

Title:
RBAP96 Mediates Radiosensitivity of Breast Cancer Cells via Interacting with Retinoblastoma Protein
作者:
Junling Zhang;  Xiaolei Xue;  Qinghui Meng;  Lu Lu;  Ming Cui;  Saijun Fan
Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300192, China;Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington DC 20079, USA
Author(s):
Junling Zhang;  Xiaolei Xue;  Qinghui Meng;  Lu Lu;  Ming Cui;  Saijun Fan
Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300192, China;Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington DC 20079, USA
关键词:
RBAP96; Retinoblasloma protein; Breast neoplasms; Transcription repression; Radiation tolerance
Keywords:
RBAP96; Retinoblasloma protein; Breast neoplasms; Transcription repression; Radiation tolerance
DOI:
10.3760/cma.j.issn.1673-4114.2016.05.001
摘要:
Objective To identify a novel retinoblastoma protein(RB)-associated protein(RBAP 96) and to explore the impact of RBAP96 on radiosensitivity of human breast cancer cells. Methods An in vivo and in vitro association of RBAP96 with RB was determined by immunoprecipitation-Western blotting and GST pull-down assay. Protein expression was measured by Western blot assay. Cellular survival was evaluated by using a colony formation assay. Results In both in vitro and in vivo assays, we found that the RBAP96 and RB interaction required a 513LXCXE517 motif on the RBAP96 protein and an intact A/B binding pocket of RB. RBAP96 enhances RB-mediated transcriptional repression. Finally, enforced expression of RBAP96 caused an elevated radiosensitivity of human breast cancer cells bearing wtRB, but did not affect radiosensitivity of breast cancer cells bearing mutant RB. Expression of a full-length RBAP96 with an 513LXCXE517 inactivating mutation(LXCXE→RXRXH) failed to result in any radiosensitivity alteration. Conclusion This study for the first time characterizes a novel RB-interacting protein RBAP96 and demonstrates that enforced expression of RBAP96 causes an increase of RBAP96-mediated transcription activation and radiosensitivity via a RB-interacting dependent manner.
Abstract:
Objective To identify a novel retinoblastoma protein(RB)-associated protein(RBAP 96) and to explore the impact of RBAP96 on radiosensitivity of human breast cancer cells. Methods An in vivo and in vitro association of RBAP96 with RB was determined by immunoprecipitation-Western blotting and GST pull-down assay. Protein expression was measured by Western blot assay. Cellular survival was evaluated by using a colony formation assay. Results In both in vitro and in vivo assays, we found that the RBAP96 and RB interaction required a 513LXCXE517 motif on the RBAP96 protein and an intact A/B binding pocket of RB. RBAP96 enhances RB-mediated transcriptional repression. Finally, enforced expression of RBAP96 caused an elevated radiosensitivity of human breast cancer cells bearing wtRB, but did not affect radiosensitivity of breast cancer cells bearing mutant RB. Expression of a full-length RBAP96 with an 513LXCXE517 inactivating mutation(LXCXE→RXRXH) failed to result in any radiosensitivity alteration. Conclusion This study for the first time characterizes a novel RB-interacting protein RBAP96 and demonstrates that enforced expression of RBAP96 causes an increase of RBAP96-mediated transcription activation and radiosensitivity via a RB-interacting dependent manner.

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备注/Memo

备注/Memo:
收稿日期:2016-08-18
基金项目:National Natural Science Foundation of China(81071906, 81172127, 81572969, 81402633); Technology and Development and Research Projects for Research Institutes, Ministry of Science and Technology(2014EG150134); Tianjin Science & Technology Pillar Program(14ZCZDSY00001); Natural Science Foundation of Tianjin(16JCQNJC13600); Peking Union Medical College Youth Innovation Fund(1581); IRM-CAMS Research Fund(1614)
通讯作者:Fan SJ, Email:fansaijun@irm-cams.ac.cn
更新日期/Last Update: 1900-01-01