The transcription factor CBFB suppresses breast cancer through orchestrating translation and transcription

Navdeep Malik, Hualong Yan, Nellie Moshkovich, Murali Palangat, Howard Yang, Vanesa Sanchez, Zhuo Cai, Tyler J. Peat, Shunlin Jiang, Chengyu Liu, Maxwell Lee, Beverly A. Mock, Stuart H. Yuspa, Daniel Larson, Lalage M. Wakefield and Jing Huang ()
Additional contact information
Navdeep Malik: Center for Cancer Research, National Cancer Institute, National Institutes of Health
Hualong Yan: Center for Cancer Research, National Cancer Institute, National Institutes of Health
Nellie Moshkovich: Center for Cancer Research, National Cancer Institute, National Institutes of Health
Murali Palangat: National Cancer Institute, National Institutes of Health
Howard Yang: Center for Cancer Research, National Cancer Institute, National Institutes of Health
Vanesa Sanchez: Center for Cancer Research, National Cancer Institute, National Institutes of Health
Zhuo Cai: Center for Cancer Research, National Cancer Institute, National Institutes of Health
Tyler J. Peat: Center for Cancer Research, National Cancer Institute, National Institutes of Health
Shunlin Jiang: Center for Cancer Research, National Cancer Institute, National Institutes of Health
Chengyu Liu: Lung, and Blood Institute, National Institutes of Health
Maxwell Lee: Center for Cancer Research, National Cancer Institute, National Institutes of Health
Beverly A. Mock: Center for Cancer Research, National Cancer Institute, National Institutes of Health
Stuart H. Yuspa: Center for Cancer Research, National Cancer Institute, National Institutes of Health
Daniel Larson: National Cancer Institute, National Institutes of Health
Lalage M. Wakefield: Center for Cancer Research, National Cancer Institute, National Institutes of Health
Jing Huang: Center for Cancer Research, National Cancer Institute, National Institutes of Health

Nature Communications, 2019, vol. 10, issue 1, 1-15

Abstract: Abstract Translation and transcription are frequently dysregulated in cancer. These two processes are generally regulated by distinct sets of factors. The CBFB gene, which encodes a transcription factor, has recently emerged as a highly mutated driver in a variety of human cancers including breast cancer. Here we report a noncanonical role of CBFB in translation regulation. RNA immunoprecipitation followed by deep sequencing (RIP-seq) reveals that cytoplasmic CBFB binds to hundreds of transcripts and regulates their translation. CBFB binds to mRNAs via hnRNPK and enhances translation through eIF4B, a general translation initiation factor. Interestingly, the RUNX1 mRNA, which encodes the transcriptional partner of CBFB, is bound and translationally regulated by CBFB. Furthermore, nuclear CBFB/RUNX1 complex transcriptionally represses the oncogenic NOTCH signaling pathway in breast cancer. Thus, our data reveal an unexpected function of CBFB in translation regulation and propose that breast cancer cells evade translation and transcription surveillance simultaneously through downregulating CBFB.

Date: 2019
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DOI: 10.1038/s41467-019-10102-6

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