BAG2 is a target of the c-Myc gene and is involved in cellular senescence via the p21CIP1 pathway

Zhang, Ju; Lou, Xiaomin; Yang, Shangbin; He, Shun; Yang, Lei; Liu, Mei; Zhu, Hongxia; Shan, Qiang; Su, Siyuan; Zhan, Qimin; Xu, Ningzhi; Liu, Siqi

doi:10.1016/j.canlet.2011.11.033

« Previous Next »Cancer Letters
Volume 318, Issue 1 , Pages 34-41, 1 May 2012

BAG2 is a target of the c-Myc gene and is involved in cellular senescence via the p21^CIP1 pathway

Ju Zhang
- Laboratory of Synthetic Biology, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 101318, China
Xiaomin Lou
- Laboratory of Synthetic Biology, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 101318, China
Shangbin Yang
- Laboratory of Cell and Molecular Biology, Cancer Institute and Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
- Present address: Department of Pathology, Ohio State University, Columbus, OH 43210-1218, USA
Shun He
- Laboratory of Cell and Molecular Biology, Cancer Institute and Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
Lei Yang
- Laboratory of Synthetic Biology, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 101318, China
Mei Liu
- Laboratory of Cell and Molecular Biology, Cancer Institute and Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
Hongxia Zhu
- Laboratory of Cell and Molecular Biology, Cancer Institute and Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
Qiang Shan
- Laboratory of Synthetic Biology, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 101318, China
Siyuan Su
- Laboratory of Synthetic Biology, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 101318, China
Qimin Zhan
- National Laboratory of Molecular Oncology, Cancer Institute and Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
Ningzhi Xu
- Laboratory of Cell and Molecular Biology, Cancer Institute and Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
- Corresponding authors. Tel.: +86 10 80485325; fax: +86 10 80485324 (S. Liu), tel.: +86 10 67738220; fax: +86 10 67738220 (N. Xu).
Siqi Liu
- Laboratory of Synthetic Biology, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 101318, China
- Corresponding authors. Tel.: +86 10 80485325; fax: +86 10 80485324 (S. Liu), tel.: +86 10 67738220; fax: +86 10 67738220 (N. Xu).
- Siqi Liu should be contacted prior to publication.

Received 24 July 2011; received in revised form 3 November 2011; accepted 29 November 2011. published online 30 December 2011.

Abstract

Suppression of c-Myc is likely to induce cellular senescence in many tumors with unclear mechanisms. A proteomics survey indicated that high levels of BCL2-associated athanogene 2 (BAG2) were found in response to c-Myc repression in TRE293 cells. This observation led to the investigation into the role of BAG2 in c-Myc-induced senescence. The association of the c-Myc/SP1 complex with the BAG2 promoter verified the role of c-Myc/SP1 in regulating BAG2 transcription. Furthermore, high levels of BAG2 were found to induce p21^CIP1-dependent senescence and subsequent carcinogenetic arrest, suggesting its possible role as an indirect activator of the p21^CIP1 pathway.

Keywords: BAG2, c-Myc, Senescence, SP1, p21^CIP1