C1QBP Negatively Regulates the Activation of Oncoprotein YBX1 in the Renal Cell Carcinoma As Revealed by Interactomics Analysis

The
Y-box-binding protein 1 (YBX1) plays a critical role in tumorigenesis
by promoting cell proliferation, overriding cell-cycle check points,
and enhancing genomic instability. In this study, the interactome
of YBX1 in renal cell carcinoma (RCC) was analyzed by coimmunoprecipitation
and mass spectrometry to better understand its function and regulatory
mechanism. A total of 129 proteins were identified as potential YBX1
binding partners. The interaction between the complement component
1, q subcomponent binding protein (C1QBP), and YBX1 was further confirmed
by immunoprecipitation and Western blotting. Knockdown of C1QBP enhanced
the phosphorylation of YBX1and its nuclear translocation, indicating
that C1QBP negatively regulated YBX1 activation. The clinical significance
of these two proteins was analyzed in the tissues from 52 RCC patients
by immunohistochemistry. Expression of YBX1 was markedly elevated
in the carcinoma tissues, and its nuclear expression was associated
with histological T stage and metastasis. Meanwhile, the level of
C1QBP in the carcinoma tissues was significantly lower than that in
the adjacent healthy tissues, which was negatively correlated with
the nuclear localization of YBX1 in the RCC tissues (P = 0.011). These data suggest that C1QBP is a novel regulator of
YBX1, and the expression of C1QBP and the nuclear expression of YBX1
could both be used as independent prognostic makers for cancer progression
in the RCC patients. The proteomics data have been deposited to the
ProteomeXchange with identifier PXD001493.