RBCK1 promotes p53 degradation via ubiquitination in renal cell carcinoma

Sifan Yu,Lu Yang,Yan Kong,Xinan Sheng,Zhihong Chi,Lu Si,Jun Guo,Tianxiao Xu,Meng Ma,Huan Tang,Chuanliang Cui,Jie Dai

doi:10.1038/s41419-019-1488-2

Sifan Yu, Lu Yang + Show 10 more

Open Access

https://doi.org/10.1038/s41419-019-1488-2

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Abstract

Renal cell carcinoma (RCC) accounts for approximately 3% of adult malignancies, and the incidence of RCC continues to rise worldwide. Although RCC can be treated with surgery at an early stages, the five-year survival rates have been observed to decline dramatically in patients with advanced disease. Most patients with RCC treated with cytotoxic or targeted drugs will develop resistance at some point during therapy. Thus, it is necessary to identify novel therapeutic targets for RCC. Here, we found that RANBP2-type and C3HC4-type zinc finger-containing 1 (RBCK1) expression was upregulated in human RCC samples. Analysis of multiple public databases revealed the correlation between RBCK1 expression and poor prognosis in RCC patients. Subsequently, we performed RBCK1 depletion experiments in RCC cells that severely affected the in vivo and in vitro proliferation of renal cancer cells. The effects of RBCK1 on cell proliferation could be rescued with p53 expression knockdown in two cell lines expressing wild-type p53. Further experiments demonstrated that RBCK1 could facilitate p53 poly-ubiquitination and degradation by direct interaction with p53. Together, our results show that RBCK1 may serve as a promising target for RCC therapy by restoring p53 functions.

Highlights

Renal cell carcinoma (RCC) represents 2 to 3% of all cancers and is the tenth most common cancer worldwide[1,2]
RBCK1 is overexpressed in renal cancer and its expression correlates with poor survival in RCC patients
Caki-1 cells were harvested with NP-40 lysis buffer

Summary

Introduction

Renal cell carcinoma (RCC) represents 2 to 3% of all cancers and is the tenth most common cancer worldwide[1,2]. We performed RNA sequencing (RNA-seq) in RCC cells after RBCK1 depletion. RNA-seq data revealed that RBCK1 could serve as a novel regulator of p53 in RCC cells.

Results

Conclusion