Abstract
The oncoprotein c-Myc is a key transcription factor with essential functions in the nucleolus (NO) to regulate ribosomal RNA (rRNA) synthesis, ribosome biogenesis, and cell proliferation. Yet, the mechanism that regulates the distribution and function of nucleolar c-Myc is still not completely understood. In this study, we identified nucleolar protein ENBA1 binding protein 2 (EBP2) as a novel functional binding partner of c-Myc. We found that coexpression of EBP2 markedly relocalized c-Myc from the nucleus to the NO, whereas depletion of EBP2 reduced the nucleolar distribution of c-Myc. Further study indicated that EBP2 is a direct binding partner of c-Myc and can block the degradation of c-Myc in a FBW7 (F-box and WD repeat domain containing 7)-independent manner. Moreover, EBP2 is a transcriptional target of c-Myc. c-Myc can bind to the promoter of EBP2 and positively regulate the EBP2 expression. Both protein and mRNA levels of EBP2 are upregulated in lung cancer samples and positively correlated with c-Myc expression. Functionally, EBP2 promotes c-Myc-mediated rRNA synthesis and cell proliferation. Collectively, our study indicates that EBP2 is a novel binding partner of c-Myc that regulates the function of nucleolar c-Myc, cell proliferation, and tumorigenesis via a positive feedback loop.
Highlights
The function of c-Myc in the NO is tightly controlled by protein degradation and its binding proteins.[10]
Discussion c-Myc has essential functions in the NO to regulate the synthesis of ribosomal RNA (rRNA), RNA polymerase I activity, and cell proliferation.[35]
We found that ENBA1 binding protein 2 (EBP2) can directly bind to c-Myc and regulate the c-Myc nucleolar localization, cell proliferation, and rRNA transcription
Summary
The function of c-Myc in the NO is tightly controlled by protein degradation and its binding proteins.[10]. ENBA1 binding protein 2 (EBP2) is originally identified as a binding protein of Epstein–Barr virus (EBV) nuclear antigen 1 that is important for EBV segregation.[13,14] Yeast homolog EBP2 (Ebp2p) is an essential nucleolar protein required for pre-ribosomal RNA (rRNA) processing and ribosomal subunit assembly.[15,16,17,18] In mammalian cells, EBP2 interacts with nucleostemin and is localized to the NO.[19] human EBP2 is associated with chromosome in mitosis.[20] Overexpression of EBP2 has been shown to be able to promote the cell proliferation and chromosome instability of 293 cells or NIH3T3 cells.[21,22] A recent study demonstrates that EBP2 is essential for the nucleolar localization of Fbw7g via direction interaction.[23] the biological functions of mammal EBP2, such as whether it may affect the stability of Fbw7g substrates, remain not completely understood. Received 26.8.13; revised 16.11.13; accepted 26.11.13; Edited by G Melino cell proliferation through c-Myc and identified that EBP2 may be a novel therapeutic target to cancers
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
