FBXO32 Targets c-Myc for Proteasomal Degradation and Inhibits c-Myc Activity

Mei, Zhichao; Zhang, Dawei; Hu, Bo; Wang, Jing; Shen, Xian; Xiao, Wuhan

doi:10.1074/jbc.m115.645978

Cited by 70 publications

(60 citation statements)

References 47 publications

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“…The tumorigenesis ability of E3 ubiquitin ligase is also emerging with defined biological activities. Several E3 ubiquitin ligase, including NEDD4 5, 10, ITCH 11, WWP2 12, 13, and FBXO32 6 have been confirmed to be related with the tumorigenesis. In order to find the tongue cancer‐related E3 ligases, we screened the human E3 ubiquitin ligase library and found the candidate molecule, RNF126.…”

Section: Discussionmentioning

confidence: 97%

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E3 Ubiquitin ligase RNF126 regulates the progression of tongue cancer

Wang

Zhao

et al. 2016

Cancer Medicine

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This study aims to analyze the role of RNF126 in the oncogenesis of tongue cancer. The cell proliferation and viability of human tongue cancer cells, SCC25 and SCC9 cells, were determined by cell counting and MTT assay, respectively. The effect of RNF126 on regulating AKT signaling pathway was analyzed through western blotting. The transplantation tumor model of nude mice was used to evaluate the tumorigenecity of RNF126. Knockdown of RNF126 inhibited the proliferation and viability of SCC9 and SCC25 cells. Inhibition of RNF126 also decreased the activity of AKT1 as well as its downstream molecules. Furthermore, RNF126 regulated the tumor volume on mice model. These data suggested that RNF126 might be related to the progression of tongue cancer through regulating AKT signaling pathway.

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Section: Discussionmentioning

confidence: 97%

“…The aberrant accumulation of oncoprotein which results from the abnormal proteolysis, contributes to the origination and progression of cancer. Previous studies have suggested that E3 ubiquitin ligase were involved in the occurrence of lung cancer, breast cancer, and oral cancer 5, 6.…”

Section: Introductionmentioning

confidence: 99%

E3 Ubiquitin ligase RNF126 regulates the progression of tongue cancer

Wang

Zhao

et al. 2016

Cancer Medicine

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“…Further research indicated that, in vivo, the size of tumor was significant reduced after intratumoral administration of the cholesterol-conjugated miR-197 mimics, which emphasized the role of miR-197 in tumor suppression (Li et al, 2006b). In addition, with overexpression miR-197, c-Myc, Bcl-2 and MMP-2, three of which are downstream targets of IL-6/STAT3 signaling pathway and tightly related to cancers (Martinou and Youle, 2011;Mei et al, 2015;Ma et al, 2015), decreased distinctly .…”

Section: Mir-197 In Tumor Suppressorsmentioning

confidence: 94%

miR-197: A novel biomarker for cancers

Wang

Chen

et al. 2016

Gene

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“…31,32 In addition, a recent study identified the classic oncogene c-Myc as an ubiquitination substrate of FBXO32, supporting the speculation that FBXO32 acts as a tumor suppressor in cancer development. 33 Currently, the role of FBXO32 in tumorigenesis still remains unclear, and the underlying mechanism is poorly understood.…”

Section: Introductionmentioning

confidence: 99%

FBXO32 suppresses breast cancer tumorigenesis through targeting KLF4 to proteasomal degradation

et al. 2017

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Krüppel-like factor 4 (KLF4, GKLF) is a zinc-finger transcription factor involved in a large variety of cellular processes, including apoptosis, cell cycle progression, as well as stem cell renewal. KLF4 is critical for cell fate decision and has an ambivalent role in tumorigenesis. Emerging data keep reminding us that KLF4 dysregulation either facilitates or impedes tumor progression, making it important to clarify the regulating network of KLF4. Like most transcription factors, KLF4 has a rather short half-life within the cell and its turnover must be carefully orchestrated by ubiquitination and ubiquitin–proteasome system. To better understand the mechanism of KLF4 ubiquitination, we performed a genome-wide screen of E3 ligase small interfering RNA library based on western blot and identified SCF-FBXO32 to be a new E3 ligase, which is responsible for KLF4 ubiquitination and degradation. The F-box domain is critical for FBXO32-dependent KLF4 ubiquitination and degradation. Furthermore, we demonstrated that FBXO32 physically interacts with the N-terminus (1–60 aa) of KLF4 via its C-terminus (228–355 aa) and directly targets KLF4 for ubiquitination and degradation. We also found out that p38 mitogen-activated protein kinase pathway may be implicated in FBXO32-mediated ubiquitination of KLF4, as p38 kinase inhibitor coincidently abrogates endogenous KLF4 ubiquitination and degradation, as well as FBXO32-dependent exogenous KLF4 ubiquitination and degradation. Finally, FBXO32 inhibits colony formation in vitro and primary tumor initiation and growth in vivo through targeting KLF4 into degradation. Our findings thus further elucidate the tumor-suppressive function of FBXO32 in breast cancer. These results expand our understanding of the posttranslational modification of KLF4 and of its role in breast cancer development and provide a potential target for diagnosis and therapeutic treatment of breast cancer.

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FBXO32 Targets c-Myc for Proteasomal Degradation and Inhibits c-Myc Activity

Cited by 70 publications

References 47 publications

E3 Ubiquitin ligase RNF126 regulates the progression of tongue cancer

E3 Ubiquitin ligase RNF126 regulates the progression of tongue cancer

miR-197: A novel biomarker for cancers

FBXO32 suppresses breast cancer tumorigenesis through targeting KLF4 to proteasomal degradation

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