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Updated: Oct 13, 2025

In Vivo Detection and Analysis of Rb Protein SUMOylation in Human Cells
Published on: November 2, 2017
HELZ2 promotes K63-linked polyubiquitination of c-Myc to induce retinoblastoma tumorigenesis
Hanjun Dai1, Wen Zeng2, Weijuan Zeng2
1Department of Ophthalmology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, People's Republic of China. daihanjun@whu.edu.cn.
Abstract:
Retinoblastoma is a rare ocular tumor in children that originates in the retina. Several core transcriptional regulators maintain the expansion of retinoblastoma tumors, including c-Myc. Here, we demonstrated that Helicase with zinc finger domain 2 (HELZ2) promoted retinoblastoma tumorigenesis by targeting c-Myc. HELZ2-deficient inhibited retinoblastoma cell proliferation, whereas overexpression of HELZ2 promoted retinoblastoma cell proliferation. In addition, high levels of HELZ2 promoted xenograft retinoblastoma tumorigenesis and inhibited animal survival. Mechanistically, HELZ2 interacted with c-Myc and promoted its K63-linked polyubiquitination. We indicated that HELZ2 promoted the interaction between E3 ubiquitin ligase HUWE1 and c-Myc, and HELZ2-mediated K63-linked polyubiquitination and activation of c-Myc were dependent on HUWE1. Taken together, HELZ2 plays a critical role in the regulation of retinoblastoma tumorigenesis by enhancing the activity of c-Myc.
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