Cereblon Promotes the Ubiquitination and Proteasomal Degradation of Interleukin Enhancer-Binding Factor 2

Lian, Qihui; Gao, Yuan; Li, Qian; He, Xian; Jiang, Xiaogang; Pu, Zhongjian; Xu, Guoqiang

doi:10.1007/s10930-020-09918-9

Cited by 2 publications

(2 citation statements)

References 56 publications

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“…In addition, our results showed that the interaction between HNRNPK and ILF2 leads to a decrease in the ubiquitination of ILF2, thereby increasing its stability. Although previous research has shown that CRBN modulates the ubiquitination of ILF2 [ 47 ], our study significantly extends the current understanding of the regulatory mechanisms underlying ILF2 protein stability.…”

Section: Discussionsupporting

confidence: 54%

LINC00571 drives tricarboxylic acid cycle metabolism in triple-negative breast cancer through HNRNPK/ILF2/IDH2 axis

Xi,

Huang,

et al. 2024

J Exp Clin Cancer Res

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Background Triple-negative breast cancer is a complex breast malignancy subtype characterized by poor prognosis. The pursuit of effective therapeutic approaches for this subtype is considerably challenging. Notably, recent research has illuminated the key role of the tricarboxylic acid cycle in cancer metabolism and the complex landscape of tumor development. Concurrently, an emerging body of evidence underscores the noteworthy role that long non-coding RNAs play in the trajectory of breast cancer development. Despite this growing recognition, the exploration of whether long non-coding RNAs can influence breast cancer progression by modulating the tricarboxylic acid cycle has been limited. Moreover, the underlying mechanisms orchestrating these interactions have not been identified. Methods The expression levels of LINC00571 and IDH2 were determined through the analysis of the public TCGA dataset, transcriptome sequencing, qRT‒PCR, and Western blotting. The distribution of LINC00571 was assessed using RNA fluorescence in situ hybridization. Alterations in biological effects were evaluated using CCK-8, colony formation, EdU, cell cycle, and apoptosis assays and a tumor xenograft model. To elucidate the interaction between LINC00571, HNRNPK, and ILF2, RNA pull-down, mass spectrometry, coimmunoprecipitation, and RNA immunoprecipitation assays were performed. The impacts of LINC00571 and IDH2 on tricarboxylic acid cycle metabolites were investigated through measurements of the oxygen consumption rate and metabolite levels. Results This study revealed the complex interactions between a novel long non-coding RNA (LINC00571) and tricarboxylic acid cycle metabolism. We validated the tumor-promoting role of LINC00571. Mechanistically, LINC00571 facilitated the interaction between HNRNPK and ILF2, leading to reduced ubiquitination and degradation of ILF2, thereby stabilizing its expression. Furthermore, ILF2 acted as a transcription factor to enhance the expression of its downstream target gene IDH2. Conclusions Our study revealed that the LINC00571/HNRNPK/ILF2/IDH2 axis promoted the progression of triple-negative breast cancer by regulating tricarboxylic acid cycle metabolites. This discovery provides a novel theoretical foundation and new potential targets for the clinical treatment of triple-negative breast cancer.

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Section: Discussionsupporting

confidence: 54%

LINC00571 drives tricarboxylic acid cycle metabolism in triple-negative breast cancer through HNRNPK/ILF2/IDH2 axis

Xi,

Huang,

et al. 2024

J Exp Clin Cancer Res

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“…It has been shown that the CUL4-RBX1-DDB1-CRBN (CRL4 CRBN ) E3 ubiquitin ligase complex regulates ILF2 turnover. 41 Thus, we examined the effect of the PRMT1/PRMT6 heteromer on the recruitment of ILF2 into CRL4 CRBN complex. The levels of ILF2 coprecipitated with CUL4A was increased in the absence of PRMT1 or PRMT6 ( Figure 8 E).…”

Section: Resultsmentioning

confidence: 99%

Cooperation between PRMT1 and PRMT6 drives lung cancer health disparities among Black/African American men

Wu,

Van Scoyk,

McHale

et al. 2024

iScience

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Cereblon Promotes the Ubiquitination and Proteasomal Degradation of Interleukin Enhancer-Binding Factor 2

Cited by 2 publications

References 56 publications

LINC00571 drives tricarboxylic acid cycle metabolism in triple-negative breast cancer through HNRNPK/ILF2/IDH2 axis

LINC00571 drives tricarboxylic acid cycle metabolism in triple-negative breast cancer through HNRNPK/ILF2/IDH2 axis

Cooperation between PRMT1 and PRMT6 drives lung cancer health disparities among Black/African American men

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