Abstract
C23 is an abundant and multi-functional protein, which plays an important role in various biological processes, including ribosome biogenesis and maturation, cell cycle checkpoints and transcriptional regulation [1, 2]. However, the role of C23 in controlling tumorigenesis has not been well defined. Here we report that C23 is highly expressed in cancer cells and the elevated expression of C23 facilitates cancer cell proliferation in vitro and tumor xenograft growth in vivo. Notably, C23 binds to p53 through its GAR domain and suppresses the transcriptional activity of p53 under DNA damage and hypoxia. Moreover, the GAR domain is critical for C23-mediated tumor cell proliferation both in vitro and in vivo. Our findings reveal a novel role of C23 in tumorigenesis and suggest that C23 may represent a potential therapeutic target for treating malignancy.
Highlights
P53, the most renowned tumor suppressor, is activated in response to a wide range of cellular stress including DNA damage, oncogene activation and hypoxia [3,4,5]
The results revealed that the C23 expression levels were frequently upregulated in cancer cell lines in comparison with the normal cell line (Figure 1A)
The data demonstrated that C23 was highly expressed in cancer lesions and cancer cell lines, which may indicate the important role of C23 in human tumor progression
Summary
P53, the most renowned tumor suppressor, is activated in response to a wide range of cellular stress including DNA damage, oncogene activation and hypoxia [3,4,5]. The gene encoding p53 undergoes inactivating mutations in >50% of human cancers and mutations≥ 18,000 in many different cancers These mutations are mainly found in the core region of p53 DNA binding domain (residues 98-292), rendering tumor genesis [10, 11]. Given the diversity and complexity of the binding partners of p53, discovering the underlying collaborators and/or regulators of p53 is still a priority for fully understanding the tumor suppressive role of p53. We demonstrate that C23 binds to p53 through its GAR domain and suppresses its transcriptional activity under hypoxia and DNA damage condition. We propose that C23 is an important regulator in tumorigenesis
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