TY - JOUR
T1 - KLF12 promotes the proliferation of breast cancer cells by reducing the transcription of p21 in a p53-dependent and p53-independent manner
AU - Li, Yanan
AU - Li, Shujing
AU - Shi, Xiaoxia
AU - Xin, Zhiqiang
AU - Yang, Yuxi
AU - Zhao, Binggong
AU - Li, Yvlin
AU - Lv, Linlin
AU - Ren, Ping
AU - Wu, Huijian
N1 - Funding Information: The pGL3-p53-reporter construct (p53-Luc) was a gift kindly provided by Professor Liu Yong Zhong (Shanghai Jiao Tong University School of Medicine). Flag-p53K370/372/373Rand Flag-p53K381/382/383Rwere gifts kindly given by Professor Tian (State Key Laboratory of Proteomics, Beijing Proteome, Research Center, National Center for Protein Sciences). We thank Dr. Alan K. Chang for his devoted effort in editing the manuscript during its preparation. Funding Information: The study was supported by the National Natural Science Foundation of China (No. 58481872263 to HW) and Liaoning Province Applied Basic Research Program Project (2023JH2/101300068 to PR). Publisher Copyright: © 2023, The Author(s).
PY - 2023/5/1
Y1 - 2023/5/1
N2 - Breast cancer is the most common cancer affecting women worldwide. Many genes are involved in the development of breast cancer, including the Kruppel Like Factor 12 (KLF12) gene, which has been implicated in the development and progression of several cancers. However, the comprehensive regulatory network of KLF12 in breast cancer has not yet been fully elucidated. This study examined the role of KLF12 in breast cancer and its associated molecular mechanisms. KLF12 was found to promote the proliferation of breast cancer and inhibit apoptosis in response to genotoxic stress. Subsequent mechanistic studies showed that KLF12 inhibits the activity of the p53/p21 axis, specifically by interacting with p53 and affecting its protein stability via influencing the acetylation and ubiquitination of lysine370/372/373 at the C-terminus of p53. Furthermore, KLF12 disrupted the interaction between p53 and p300, thereby reducing the acetylation of p53 and stability. Meanwhile, KLF12 also inhibited the transcription of p21 independently of p53. These results suggest that KLF12 might have an important role in breast cancer and serve as a potential prognostic marker and therapeutic target.
AB - Breast cancer is the most common cancer affecting women worldwide. Many genes are involved in the development of breast cancer, including the Kruppel Like Factor 12 (KLF12) gene, which has been implicated in the development and progression of several cancers. However, the comprehensive regulatory network of KLF12 in breast cancer has not yet been fully elucidated. This study examined the role of KLF12 in breast cancer and its associated molecular mechanisms. KLF12 was found to promote the proliferation of breast cancer and inhibit apoptosis in response to genotoxic stress. Subsequent mechanistic studies showed that KLF12 inhibits the activity of the p53/p21 axis, specifically by interacting with p53 and affecting its protein stability via influencing the acetylation and ubiquitination of lysine370/372/373 at the C-terminus of p53. Furthermore, KLF12 disrupted the interaction between p53 and p300, thereby reducing the acetylation of p53 and stability. Meanwhile, KLF12 also inhibited the transcription of p21 independently of p53. These results suggest that KLF12 might have an important role in breast cancer and serve as a potential prognostic marker and therapeutic target.
UR - http://www.scopus.com/inward/record.url?scp=85158079266&partnerID=8YFLogxK
U2 - https://doi.org/10.1038/s41419-023-05824-x
DO - https://doi.org/10.1038/s41419-023-05824-x
M3 - Article
C2 - 37156774
SN - 2041-4889
VL - 14
JO - Cell Death & Disease
JF - Cell Death & Disease
IS - 5
M1 - 313
ER -