The ubiquitin-interacting motif of 26S proteasome subunit S5a induces A549 lung cancer cell death

Elangovan, Muthukumar; Choi, Eun Seo; Jang, Bong Geom; Kim, Mi Sun; Yoo, Yung Joon

doi:10.1016/j.bbrc.2007.09.127

Cited by 8 publications

(3 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, immunoprecipitated complexes of UXT from LOX‐PP expressing cells contained ubiquitin residues, confirming that LOX‐PP is targeting UXT to the proteasome for degradation. In support of this notion, Mass Spectrometry analysis of LOX‐PP co‐precipitating proteins recently identified PSMD2 and PSMD4, two components of the 26S proteasome that are docking sites for polyubiquitinated proteins [Elangovan et al, ; Matsuyama et al, ], as proteins that associate with ectopically expressed LOX‐PP in HEK293 cells (Seiichi Sato and GES, unpublished observations) [Sato et al, ]. Moreover, it has been suggested that the downregulation of UXT expression in prostate cancer might be occurring by changes in translation and/or degradation of UXT [Nwachukwu et al, ].…”

Section: Discussionmentioning

confidence: 99%

UXT Is a LOX-PP Interacting Protein That Modulates Estrogen Receptor Alpha Activity in Breast Cancer Cells

et al. 2017

View full text Add to dashboard Cite

The lysyl oxidase proenzyme propeptide region (LOX-PP) is a tumor suppressor protein whose mechanism of action is not completely understood. Here, the Ubiquitously expressed Transcript (UXT) was identified in a yeast two-hybrid assay with LOX-PP as bait and confirmed as a novel LOX-PP associating protein. UXT, a prefoldin-like protein, is ubiquitous in human and mouse. Since UXT modulates androgen receptor transcriptional activity in prostate cancer, we studied its role in breast cancer. Breast tumors and derived cell lines overexpressed UXT. UXT was able to associate with the estrogen receptor alpha (ER) and decrease its transcriptional activity and target gene expression. Conversely, UXT knockdown increased ER element-dependent transcriptional activity. Ectopic LOX-PP relocalized UXT to the cytoplasm and decreased its stability. UXT ubiquitination and depletion in the presence of LOX-PP was rescued by a proteasomal inhibitor. In summary, proteasome-mediated turnover of UXT upon interaction with LOX-PP releases repression of ER transcriptional activity. J. Cell. Biochem. 118: 2347-2356, 2017. © 2017 Wiley Periodicals, Inc.

show abstract

Section: Discussionmentioning

confidence: 99%

UXT Is a LOX-PP Interacting Protein That Modulates Estrogen Receptor Alpha Activity in Breast Cancer Cells

et al. 2017

View full text Add to dashboard Cite

show abstract

“…A recent study has demonstrated that PSMC6 overexpression could impair cell cycle progression and cell proliferation via inhibiting the PI3K/AKT signaling pathway [ 18 ]. Meanwhile, S5aC, a multiubiquitin binding component of the 19S RP, is found capable of inducing A549 lung cancer cell death [ 19 ]. Therefore, a closer investigation of genes related to the 26S proteasome in lung cancer shall provide detailed information on the cellular functions of those subunits in lung cancer carcinogenesis and reveal potential therapeutic targets.…”

Section: Introductionmentioning

confidence: 99%

The Silence of PSMC6 Inhibits Cell Growth and Metastasis in Lung Adenocarcinoma

Zhang

Shi

Liao

et al. 2021

BioMed Research International

View full text Add to dashboard Cite

The proteasome has been validated as an anticancer drug target, while the role of a subunit of proteasome, PSMC6, in lung adenocarcinoma (LUAD) has not been fully unveiled. In this study, we observed that both the RNA and protein of PSMC6 were highly upregulated in LUAD compared with the adjacent normal tissues. Moreover, a high PSMC6 expression was associated with poor prognosis. In accordance with this finding, PSMC6 was associated with poor tumor differentiation. Furthermore, the silence of PSMC6 by small interference RNAs (siRNAs) could significantly inhibit cell growth, migration, and invasion in lung cancer cell lines, suggesting that PSMC6 might serve as a promising therapeutic target in LUAD. To further explore the molecular mechanism of PSMC6 in LUAD, we observed that the proteasome subunits, such as PSMD10, PSMD6, PSMD9, PSMD13, PSMB3, PSMB1, PSMA4, PSMC1, PSMC2, PSMD7, and PSMD14, were highly correlated with PSMC6 expression. Based on the gene set enrichment analysis, we observed that these proteasome subunits were involved in the degradation of AXIN protein. The correlation analysis revealed that the positively correlated genes with PSMC6 were highly enriched in WNT signaling-related pathways, demonstrating that the PSMC6 overexpression may activate WNT signaling via degrading the AXIN protein, thereby promoting tumor progression. In summary, we systematically evaluated the differential expression levels and prognostic values of PSMC6 and predicted its biological function in LUAD, which suggested that PSMC6 might act as a promising therapeutic target in LUAD.

show abstract

“…This regional and ethnic characteristic was determined to be strongly associated with genetic factors [6]. Polymorphism of R4810K in the RING (encoded by the Really Interesting New Gene 1) [7] finger protein RNF213 was proposed to be the strongest susceptible gene of MMD and mediate the protein-protein interactions and have ubiquitin-protein ligase activity [8,9]. However, not all patients with MMD have the RNF213 variant, which indicates that the pathology of MMD is a complex pathway that includes genetic factors, environmental factors, and an innate angiogenetic capacity [10,11].…”

Section: Introductionmentioning

confidence: 99%

Pathological Circulating Factors in Moyamoya Disease

Fang

Wei

et al. 2021

IJMS

View full text Add to dashboard Cite

Moyamoya disease (MMD) is a cerebrovascular disease that presents with vascular stenosis and a hazy network of collateral formations in angiography. However, the detailed pathogenic pathway remains unknown. Studies have indicated that in addition to variations in the of genetic factor RNF213, unusual circulating angiogenetic factors observed in patients with MMD may play a critical role in producing “Moyamoya vessels”. Circulating angiogenetic factors, such as growth factors, vascular progenitor cells, cytokines, inflammatory factors, and other circulating proteins, could promote intimal hyperplasia in vessels and excessive collateral formation with defect structures through endothelial hyperplasia, smooth muscle migration, and atypical neovascularization. This study summarizes the hypothesized pathophysiology of how these circulating factors affect MMD and the interactive modulation between them.

show abstract

The ubiquitin-interacting motif of 26S proteasome subunit S5a induces A549 lung cancer cell death

Cited by 8 publications

References 27 publications

UXT Is a LOX-PP Interacting Protein That Modulates Estrogen Receptor Alpha Activity in Breast Cancer Cells

UXT Is a LOX-PP Interacting Protein That Modulates Estrogen Receptor Alpha Activity in Breast Cancer Cells

The Silence of PSMC6 Inhibits Cell Growth and Metastasis in Lung Adenocarcinoma

Pathological Circulating Factors in Moyamoya Disease

Contact Info

Product

Resources

About