Structural Determinants Involved in the Regulation of CXCL14/BRAK Expression by the 26 S Proteasome

Peterson, Francis C.; Thorpe, Jeffery A.; Harder, Adam; Volkman, Brian F.; Schwarze, Steven R.

doi:10.1016/j.jmb.2006.08.057

Cited by 34 publications

(35 citation statements)

References 37 publications

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“…This can be explained with the high expression level of CXCL14 in stress conditions60. Such findings prompt speculation that CXCL14 expression is induced in response to stress61. In agreement with previous studies, CXCL14 has been shown to possess functions similar to other trophic factors62, such as the activation of endogenous survival mechanisms to enhance growth and to repair neural tissue63.…”

Section: Discussionsupporting

confidence: 81%

A Crucial Role of CXCL14 for Promoting Regulatory T Cells Activation in Stroke

Lee¹,

Liu²,

Lin³

et al. 2017

Theranostics

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Inflammatory processes have a detrimental role in the pathophysiology of ischemic stroke. However, little is known about the endogenous anti-inflammatory mechanisms in ischemic brain. Here, we identify CXCL14 as a critical mediator of these mechanisms. CXCL14 levels were upregulated in the ischemic brains of humans and rodents. Moreover, hypoxia inducible factor-1α (HIF-1α) drives hypoxia- or cerebral ischemia (CI)-dependent CXCL14 expression via directly binding to the CXCL14 promoter. Depletion of CXCL14 inhibited the accumulation of immature dendritic cells (iDC) or regulatory T cells (Treg) and increased the infarct volume, whereas the supplementation of CXCL14 had the opposite effects. CXCL14 promoted the adhesion, migration, and homing of circulating CD11c+ iDC to the ischemic tissue via the upregulation of the cellular prion protein (PrPC), PECAM-1, and MMPs. The accumulation of Treg in ischemic areas of the brain was mediated through a cooperative effect of CXCL14 and iDC-secreted IL-2-induced Treg differentiation. Interestingly, CXCL14 largely promoted IL-2-induced Treg differentiation. These findings indicate that CXCL14 is a critical immunomodulator involved in the stroke-induced inflammatory reaction. Passive CXCL14 supplementation provides a tractable path for clinical translation in the improvement of stroke-induced neuroinflammation.

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Section: Discussionsupporting

confidence: 81%

A Crucial Role of CXCL14 for Promoting Regulatory T Cells Activation in Stroke

Lee¹,

Liu²,

Lin³

et al. 2017

Theranostics

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“…Cell lysates were prepared and Western blot analysis was carried out as previously described. 15 Tumor lysates were prepared by homogenizing excised tumor tissue in extraction buffer (0.1% CHAPS, 25 mM HEPES, 5 mM EDTA, 2 mM DTT). Extracts were flash frozen in liquid nitrogen and stored at -70°C.…”

Section: Methodsmentioning

confidence: 99%

Velcade sensitizes prostate cancer cells to TRAIL induced apoptosis and suppresses tumor growth in vivo

Christian

Thorpe²,

Schwarze³

2009

Cancer Biology & Therapy

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Inducing apoptosis via the extrinsic death receptor pathway is an attractive anti-cancer treatment strategy, however, numerous cancer cells exhibit significant resistance to death ligand stimuli. Here, we investigated the anti-neoplastic capability of proteasome inhibition, through the administration of Velcade, to synergize with a death receptor agonist in vivo. The death ligand-resistant LNCaP prostate xenograft model was utilized. Tumors were established and mice were treated with Velcade, TRAIL (TNF-Related Apoptosis Inducing Ligand) or the combined regimen. Only mice treated with a combination of Velcade and TRAIL was tumor growth inhibited with a corresponding loss of the hemorrhagic phenotype, decreased tumor cell proliferation and increased tumor cell apoptosis. Next, to determine if the extrinsic pathway is critical for mediating the anti-tumor efficacy that can be achieved in some cell types with Velcade treatment alone, the death receptor sensitive PC-3 xenograft model was used. PC-3 tumors exhibited a 54% decrease in tumor volume in response to Velcade, while c-FLIP overexpressing PC-3 xenografts were resistant to the treatment. These findings suggest that the extrinsic apoptotic pathway can mediate the anti-tumor effects of Velcade and support the therapeutic use of proteasome inhibition in combination with a death receptor stimulus in the treatment of prostate cancer.

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“…This mechanism is very important in terms of angiogenesis, cell migration, and metastasis, all playing enormous roles in cancer (66–69). The role of chemokines in metastasis is the outcome of modified presentation of G-protein coupled receptors.…”

Section: The 26s Proteasome Complex In Different Cellular Events and mentioning

confidence: 99%

The 26S proteasome complex: An attractive target for cancer therapy

Frankland-Searby

Bhaumik

2012

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

130

145

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The 26S proteasome complex engages in an ATP-dependent proteolytic degradation of a variety of oncoproteins, transcription factors, cell cycle specific cyclins, cyclin-dependent kinase inhibitors, ornithine decarboxylase, and other key regulatory cellular proteins. Thus, the proteasome regulates either directly or indirectly many important cellular processes. Altered regulation of these cellular events is linked to the development of cancer. Therefore, the proteasome has become an attractive target for the treatment of numerous cancers. Several proteasome inhibitors that target the proteolytic active sites of the 26S proteasome complex have been developed and tested for anti-tumor activities. These proteasome inhibitors have displayed impressive anti-tumor functions by inducing apoptosis in different tumor types. Further, the proteasome inhibitors have been shown to induce cell cycle arrest, and inhibit angiogenesis, cell-cell adhesion, cell migration, immune and inflammatory responses, and DNA repair response. A number of proteasome inhibitors are now in clinical trials to treat multiple myeloma and solid tumors. Many other proteasome inhibitors with different efficiencies are being developed and tested for anti-tumor activities. Several proteasome inhibitors currently in clinical trials have shown significantly improved anti-tumor activities when combined with other drugs such as histone deacetylase (HDAC) inhibitors, Akt (protein kinase B) inhibitors, DNA damaging agents, Hsp90 (heat shock protein 90) inhibitors, and lenalidomide. The proteasome inhibitor bortezomib is now in the clinic to treat multiple myeloma and mantle cell lymphoma. Here, we discuss the 26S proteasome complex in carcinogenesis and different proteasome inhibitors with their potential therapeutic applications in treatment of numerous cancers.

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Structural Determinants Involved in the Regulation of CXCL14/BRAK Expression by the 26 S Proteasome

Cited by 34 publications

References 37 publications

A Crucial Role of CXCL14 for Promoting Regulatory T Cells Activation in Stroke

A Crucial Role of CXCL14 for Promoting Regulatory T Cells Activation in Stroke

Velcade sensitizes prostate cancer cells to TRAIL induced apoptosis and suppresses tumor growth in vivo

The 26S proteasome complex: An attractive target for cancer therapy

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