Ubiquitination involved enzymes and cancer

Zhou, Meijuan; Chen, Fangzhi; Chen, Hanchun

doi:10.1007/s12032-014-0093-6

Cited by 43 publications

(44 citation statements)

References 95 publications

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“…Accumulating evidence has demonstrated that ubiquitination is associated with the progression of cancer [7]. There are more than 600 E3 ligases in humans, some of which regulate the expression of tumor-suppressor or tumor-promoting proteins.…”

Section: Introductionmentioning

confidence: 99%

UBE2S is associated with malignant characteristics of breast cancer cells

Ayesha¹,

Hyodo²,

Asano³

et al. 2015

Tumor Biol.

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Ubiquitination is essential for various biological processes, such as signal transduction, intracellular trafficking, and protein degradation. Accumulating evidence has demonstrated that ubiquitination plays a crucial role in cancer development. In this report, we examine the expression and function of ubiquitin-conjugating enzyme E2S (UBE2S) in breast cancer. Immunohistochemical analysis revealed that UBE2S is highly expressed in breast cancer. The depletion of UBE2S by siRNA induced disruption of the actin cytoskeleton and focal adhesions. Interestingly, phosphorylation of FAK at Tyr397, which is important for the transduction of integrin-mediated signaling, was significantly reduced by UBE2S knockdown. We also show that UBE2S knockdown suppressed the malignant characteristics of breast cancer cells, such as migration, invasion, and anchorage-independent growth. Our results indicate that UBE2S could be a potential target for breast cancer treatment.

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Section: Introductionmentioning

confidence: 99%

UBE2S is associated with malignant characteristics of breast cancer cells

Ayesha¹,

Hyodo²,

Asano³

et al. 2015

Tumor Biol.

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“…The ubiquitination process, which includes activation by ubiquitin-activating enzymes (E1s), conjugation by ubiquitin-conjugating enzymes (E2s), and ligation by ubiquitin ligases (E3s), can alter protein interactions, location, function, activity, and lifespan. It also affects the cell cycle and regulates cancer-related processes, DNA repair, and inflammation [1, 2]. Ubiquitin-conjugating enzymes (E2s), which target proteins for degradation via the proteasome, accept ubiquitin from the E1 complex and catalyze monoubiquitination.…”

Section: Introductionmentioning

confidence: 99%

UBE2T knockdown inhibits gastric cancer progression

Luo

Yao

et al. 2017

Oncotarget

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Ubiquitin-conjugating enzymes (E2 enzymes) such as UBE2T target proteins for degradation via the proteasome. Here, we examined the effects of UBE2T on the progression of gastric cancer. UBE2T was highly expressed in gastric tumors and gastric cancer cells. siRNA-mediated suppression of UBE2T inhibited gastric cancer cell proliferation and colony formation by promoting cell cycle arrest at G2/M phase and increasing apoptosis. Suppression of UBE2T also attenuated the invasive and metastatic abilities of gastric cancer cells by altering expression of epithelial-mesenchymal transition (EMT)-related factors. A xenograft model in which nude mice were injected with UBE2T knockdown human gastric cancer cells confirmed that suppression of UBE2T also decreased tumor formation and growth in vivo. Expression levels of CCND1, Phospho-GSK3B, WNT family members, and MYC were all affected by UBE2T knockdown. These results suggest that UBE2T plays a critical role in gastric cancer, and that it may serve as a useful prognostic biomarker and therapeutic target in gastric cancer patients.

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“…The functional consequences of protein ubiquitination are highly dependent on the ubiquitination pattern (monoubiquitination vs polyubiquitination) and the ubiquitination linkage types [16]. At present, eight inter-ubiquitin linkage types such as K6, K11, K27, K29, K33, K48, K63, and linear ubiquitination have been reported [17, 39, 54].…”

Section: Discussionmentioning

confidence: 99%

“…To execute the ubiquitination process, the consecutive action of three enzymes including the E1 ubiquitin-activating enzyme, the E2 ubiquitin-conjugating enzyme, and the E3 ubiquitin ligases are required for the attachment of ubiquitin to a substrate [16, 17]. The ubiquitin-proteasome system (UPS) is often utilized to fine-tune the expression of target proteins that are associated with cancer development and progression.…”

Section: Introductionmentioning

confidence: 99%

“…The ubiquitin-proteasome system (UPS) is often utilized to fine-tune the expression of target proteins that are associated with cancer development and progression. As a mechanism of quality control for protein folding, ubiquitin-dependent proteasomal degradation is often coupled with the molecular chaperone system to remove misfolded proteins [16, 18, 19]. In this system, E3 ubiquitin ligases appear to be the key regulators that function together with the chaperone system to regulate protein degradation.…”

Section: Introductionmentioning

confidence: 99%

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The E3 ubiquitin ligase CHIP mediates ubiquitination and proteasomal degradation of PRMT5

Zhang

Zeng

et al. 2016

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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Protein arginine methyltransferase 5 (PRMT5) is an important member of the protein arginine methyltransferase family that regulates many cellular processes through epigenetic control of target gene expression. Because of its overexpression in a number of human cancers and its essential role in cell proliferation, transformation, and cell cycle progression, PRMT5 has been recently proposed to function as an oncoprotein in cancer cells. However, how its expression is regulated in cancer cells remains largely unknown. We have previously demonstrated that the transcription of PRMT5 can be negatively regulated by the PKC/c-Fos signaling pathway through modulating the transcription factor NF-Y in prostate cancer cells. In the present study, we demonstrated that PRMT5 undergoes polyubiquitination, possibly through multiple lysine residues. We also identified carboxyl terminus of heat shock cognate 70-interacting protein (CHIP), an important chaperone-dependent E3 ubiquitin ligase that couples protein folding/refolding to protein degradation, as an interacting protein of PRMT5 via mass spectrometry. Their interaction was further verified by co-immuoprecipitation, GST pull-down, and bimolecular fluorescence complementation (BiFC) assay. In addition, we provided evidence that the CHIP/chaperone system is essential for the negative regulation of PRMT5 expression via K48-linked ubiquitin-dependent proteasomal degradation. Given that down-regulation of CHIP and overexpression of PRMT5 have been observed in several human cancers, our finding suggests that down-regulation of CHIP may be one of the mechanisms underlying PRMT5 overexpression in these cancers.

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Ubiquitination involved enzymes and cancer

Cited by 43 publications

References 95 publications

UBE2S is associated with malignant characteristics of breast cancer cells

UBE2S is associated with malignant characteristics of breast cancer cells

UBE2T knockdown inhibits gastric cancer progression

The E3 ubiquitin ligase CHIP mediates ubiquitination and proteasomal degradation of PRMT5

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