TRIM26 positively regulates the inflammatory immune response through K11-linked ubiquitination of TAB1

Zhao, Jian; Cai, Baoshan; Shao, Zhugui; Zhang, Lei; Zheng, Yi; Hong, Chun Pyo; Yi, Fan; Liu, Bingyu; Gao, Chengjiang

doi:10.1038/s41418-021-00803-1

Cited by 44 publications

(40 citation statements)

References 44 publications

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“…In this study, we supplemented the mechanism that UBE2S physically bound to p16 and mediated its proteasomal degradation via K11-linked ubiquitination rather than K48- or K63-linked ubiquitination in PCa. Consistent with this, UBE2S has been recognized as the specific E2-conjugating enzyme that elongates Lys11-linked polyubiquitin chains on substrates and is involved in the cell cycle, signal transduction and tumour metastasis 42 , 43 . Furthermore, our data showed that silencing p16 effectively reversed the inhibition of proliferation in UBE2S-knockdown cells, suggesting that UBE2S regulates the cell cycle in PCa in a p16-dependent manner.…”

Section: Discussionmentioning

confidence: 69%

UBE2S as a novel ubiquitinated regulator of p16 and β-catenin to promote bone metastasis of prostate cancer

Peng¹,

Chen²,

Huang³

et al. 2022

Int. J. Biol. Sci.

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Bone metastasis is the main site of metastasis and causes the most deaths in patients with prostate cancer (PCa). The mechanism of bone metastasis is complex and not fully clarified. By RNA sequencing and analysing key pathways in bone metastases of PCa, we found that one of the most important characteristics during PCa bone metastasis was G1/S transition acceleration caused by low protein levels of p16INK4a (p16). Interestingly, we demonstrated that UBE2S bound and degraded p16 through K11- rather than K48- or K63-linked ubiquitination, which accelerated PCa tumour cell G1/S transition in vivo and in vitro . Moreover, UBE2S also stabilized β-catenin through K11-linked ubiquitination, leading to enhanced migration and invasion of tumour cells in PCa bone metastasis. Based on our cohorts and public databases, UBE2S was overexpressed in bone metastases and positively correlated with a high Gleason score, advanced nodal metastasis status and poor prognosis in PCa. Finally, targeting UBE2S with cephalomannine inhibited proliferation and invasion in vitro , and bone metastasis of PCa in vivo . This study innovatively discovered that UBE2S plays an oncogenic role in bone metastasis of PCa by degrading p16 and stabilizing β-catenin via K11-linked ubiquitination, suggesting that it may serve as a multipotent target for metastatic PCa treatment.

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Section: Discussionmentioning

confidence: 69%

UBE2S as a novel ubiquitinated regulator of p16 and β-catenin to promote bone metastasis of prostate cancer

Peng¹,

Chen²,

Huang³

et al. 2022

Int. J. Biol. Sci.

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“…Trim26 (Tripartite motif-containing protein 26) is involved in protein ubiquitination and proteosomal degradation. It is regulated by CIITA (a regulator of MhcII genes) which plays a key role in antigen presentation [ 44 ] and anti-viral innate immune activation [ 45 ]. Mog (myelin oligodendrocyte glycoprotein) functions in maintaining the myelin sheath and is an important contributor to autoimmune diseases.…”

Section: Resultsmentioning

confidence: 99%

MhcII Regulates Transmission of α-Synuclein-Seeded Pathology in Mice

Cruz

Moon

et al. 2022

IJMS

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MHCII molecules, expressed by professional antigen-presenting cells (APCs) such as T cells and B cells, are hypothesized to play a key role in the response of cellular immunity to α-synuclein (α-syn). However, the role of cellular immunity in the neuroanatomic transmission of α-syn pre-formed fibrillar (PFF) seeds is undetermined. To illuminate whether cellular immunity influences the transmission of α-syn seeds from the periphery into the CNS, we injected preformed α-syn PFFs in the hindlimb of the Line M83 transgenic mouse model of synucleinopathy lacking MhcII. We showed that a complete deficiency in MhcII accelerated the appearance of seeded α-syn pathology and shortened the lifespan of the PFF-seeded M83 mice. To characterize whether B-cell and T-cell inherent MhcII function underlies this accelerated response to PFF seeding, we next injected α-syn PFFs in Rag1−/− mice which completely lacked these mature lymphocytes. There was no alteration in the lifespan or burden of endstage α-syn pathology in the PFF-seeded, Rag1-deficient M83+/− mice. Together, these results suggested that MhcII function on immune cells other than these classical APCs is potentially involved in the propagation of α-syn in this model of experimental synucleinopathy. We focused on microglia next, finding that while microglial burden was significantly upregulated in PFF-seeded, MhcII-deficient mice relative to controls, the microglial activation marker Cd68 was reduced in these mice, suggesting that these microglia were not responsive. Additional analysis of the CNS showed the early appearance of the neurotoxic astrocyte A1 signature and the induction of the Ifnγ-inducible anti-viral response mediated by MhcI in the MhcII-deficient, PFF-seeded mice. Overall, our data suggest that the loss of MhcII function leads to a dysfunctional response in non-classical APCs and that this response could potentially play a role in determining PFF-induced pathology. Collectively, our results identify the critical role of MhcII function in synucleinopathies induced by α-syn prion seeds.

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“…It is well known that TGF-β-activated kinase 1 (TAK1) binds to the adaptor protein TAB1 to mediate the activation of downstream NF-κB signaling cascades 18 . In addition, studies have shown that the TAK1-NF-κB signaling pathway plays a vital role in the progression of lymphoma and mediates tumor cell apoptosis through this signaling 19 , 20 .…”

Section: Resultsmentioning

confidence: 99%

Alizarin, a nature compound, inhibits the growth of pancreatic cancer cells by abrogating NF-κB activation

Xu¹,

Hou²,

C³

et al. 2022

Int. J. Biol. Sci.

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The current performance of nature compounds in antitumor field is gradually attracted more and more attention, we discovered a nature active ingredient alizarin possess potent natural reductive NF-κB activity to against pancreatic cancer. However, the preclinical pharmacology and therapeutic effect, and the underlying mechanisms of alizarin in inhibiting pancreatic cancer are still unclear. After high-throughput screening, this is the first report that alizarin can induce a potent inhibitory effect against pancreatic cancer cells. Alizarin induced cell cycle arrest and promoted cell apoptosis by inhibiting TNF-α-stimulated NF-κB activity and nuclear translocation, and inactivated its related TNF-α-TAK1-NF-κB signaling cascade followed by downregulation of NF-κB target genes involved in cell apoptosis (Bcl-2, Bcl-xL, XIAP) and in the cell cycle and growth (cyclin D, c-myc). Due to the abrogation of NF-κB activity, combination of alizarin and gemcitabine exerted a better inhibitory effect on pancreatic cancer. In summary, natural component alizarin, inhibited cell proliferation and induced apoptosis in vitro and in vivo through targeting of the NF-κB signaling cascade with minimal toxicity, which combine with gemcitabine, can significantly enhance the antitumor capability, playing a synergistic effect. Therefore, alizarin may play a role in reversing gemcitabine resistance caused by overactivated NF-κB in clinical application in the future.

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TRIM26 positively regulates the inflammatory immune response through K11-linked ubiquitination of TAB1

Cited by 44 publications

References 44 publications

UBE2S as a novel ubiquitinated regulator of p16 and β-catenin to promote bone metastasis of prostate cancer

UBE2S as a novel ubiquitinated regulator of p16 and β-catenin to promote bone metastasis of prostate cancer

MhcII Regulates Transmission of α-Synuclein-Seeded Pathology in Mice

Alizarin, a nature compound, inhibits the growth of pancreatic cancer cells by abrogating NF-κB activation

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