Targeting the ubiquitin-proteasome system for cancer treatment: discovering novel inhibitors from nature and drug repurposing

Soave, Claire; Guerin, Tracey; Liu, Jinbao; Dou, Q. Ping

doi:10.1007/s10555-017-9705-x

Cited by 92 publications

(63 citation statements)

References 139 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The reaction was stopped by adding 100 µM monochloroacetate and 30mM sodium acetate pH=4. that proteasome subunit beta [5] levels were significantly decreased in LSCD-CEC, when compared to healthy control CEC, indicating a decreased proteasome activity in the ocular surface. However, autophagy's proteins microtubule-associated protein 1 light chain 3 B (MA-PLC3B) ( Figure 1B) and ATG12-ATG5 complex ( Figure 1C) expressions were found elevated in LSCD-diseased CEC, when compared to control CEC, suggesting an activation of autophagy in the ocular surface with LSCD.…”

Section: Proteasome Enzyme Assaymentioning

confidence: 81%

“…Briefly, cells were grown in co-culture with mouse acterized as the "Kiss of Death" because protein substrates are tagged with ubiquitin by the ubiquitination system prior to translocation inside the proteasome catalytic chamber for degradation by beta subunits [4]. Since then, there was an explosion of publications investigating the cellular function of proteasome, and, consequently proteasome inhibitors came to the market to treat cancer and suppress tumor formation [5]. Velcade, or Bortezomib/PS341, was the first therapeutic proteasome inhibitor to be tested in humans for its activity towards hematologic malignancies.…”

Section: Proteasome and Autophagy Inhibitionmentioning

confidence: 99%

See 1 more Smart Citation

Proteasome and Autophagy Pathway in Corneal Epithelial Cells with Limbal Stem Cell Deficiency

Bardag‐Gorce¹,

Di²,

Niihara³

et al. 2020

Int J Ophthalmol Clin Res

View full text Add to dashboard Cite

Purpose: Ubiquitin proteasome pathway (UPP) failure has been reported in case of rabbit Limbal Stem Cell Deficiency (LSCD). In the present study, we examined the effect of LSCD on autophagy in comparison to LSCD's effect on UPP. Methods: Rabbits with surgically induced LSCD were used. Corneal epithelial cells (CEC) were collected to measure the levels of autophagy and UPP biomarkers. Rabbit oral epithelial cells were isolated, cultured and treated with autophagy and proteasome inhibitors. Results: Immunofluorescent staining showed that both pathways were positive in normal corneal epithelium. However, while proteasome subunits were decreased in LSCD-CEC, autophagy biomarker MAPLC3B and ATG12-ATG5 complex were significantly increased in LSCD-CEC, compared to healthy CEC. These results indicate that LSCD-induced impairment of UPP may cause a compensatory stimulation of autophagy. However, despite autophagy up regulation, damaged and unwanted proteins, such as modified keratin K4 and K13 aggregates, still deposited and accumulated in LSCD-CEC without clearance, possibly contributing to CEC haziness. Proteasome inhibition in cultured oral epithelial cell sheet caused an increase in the expression of MAPLC3B and ATG12-ATG5 complex, supporting the observation that when UPP is failing, autophagy is stimulated. When autophagy was inhibited with chloroquine, proteasome activity was significantly increased compared to untreated cells. In addition, there a slight decrease in unmodified K4 and K13 expression levels with no keratin high molecular weight deposition when autophagy was inhibited. Conclusions: We report that inhibition of autophagy leads to an activation in proteasome activity, which may stimulate protein degradation to alleviate the symptoms of LSCD.

show abstract

Section: Proteasome Enzyme Assaymentioning

confidence: 81%

Section: Proteasome and Autophagy Inhibitionmentioning

confidence: 99%

Proteasome and Autophagy Pathway in Corneal Epithelial Cells with Limbal Stem Cell Deficiency

Bardag‐Gorce¹,

Di²,

Niihara³

et al. 2020

Int J Ophthalmol Clin Res

View full text Add to dashboard Cite

show abstract

“…The ubiquitin-proteasome system (UPS) is an important signaling for regulating the degradation or function of intracellular proteins in many diseases, including tumors [18,19]. The UPS is ATP-dependent and three classes of enzymes are required for mediating protein ubiquitination, including ubiquitin-activating enzyme E1, ubiquitinconjugating enzyme E2 and ubiquitin ligase E3 [20][21][22].…”

Section: Discussionmentioning

confidence: 99%

RING finger protein 38 induces gastric cancer cell growth by decreasing the stability of the protein tyrosine phosphatase SHP‐1

Zhang

et al. 2018

FEBS Letters

View full text Add to dashboard Cite

The function of the E3 ligase RNF38 is still unknown in gastric cancer. Here, we found that RNF38 is upregulated in gastric cancer, and it is associated with the overall survival of gastric cancer patients. Further studies showed that RNF38 interacts with the nonreceptor tyrosine phosphatase SH2-containing protein tyrosine phosphatase 1 (SHP-1) and induces the polyubiquitination of SHP-1, which leads to destabilization of SHP-1 and promotion of STAT3 signaling in gastric cancer cells. In addition, overexpression or knockdown of RNF38 induces or suppresses gastric cancer cell growth in vitro, respectively, and silencing RNF38 delays tumor growth in vivo. These findings demonstrate that RNF38 is functional in gastric cancer and promotes STAT3 signaling by destabilizing SHP-1; thus, RNF38 could be a novel target for gastric cancer therapy.

show abstract

“…The ubiquitin-proteasome pathway is a multifaceted complex responsible for the regulation of proteins involved in neoplastic activity, such as cyclin-dependent kinases (CDK), BCL-2, and NFκB complex (162,163). The role of the proteasome is upregulation of these key pathways, making it a promising antineoplastic target (10,(164)(165)(166)(167)(168). Finding that PIs lead to cell cycle inhibition and apoptosis in tumor cells has pushed them to be developed as antineoplastic agents.…”

Section: Proteasome Inhibitors (Pis)mentioning

confidence: 99%

“…It is thought that the constellation of proteins whose degradation is inhibited by PI interrupts intracellular processes crucial for the survival of tumor cells. Some examples are (1) cell cycle interruption by inhibiting the degradation of CDK such as p21 and p27; (2) inhibition of the nuclear signal transduction pathway of the κB factor (which typically inhibits apoptosis) through the accumulation of the I-κB inhibitory protein; and (3) promoting apoptosis prolonging the function of the pro-apoptotic members of the Bcl-2 proteins, such as Noxa (10,(164)(165)(166)(167)(168).…”

Section: Proteasome Inhibitors (Pis)mentioning

confidence: 99%

Overview of Targeted Drugs for Mature B-Cell Non-hodgkin Lymphomas

et al. 2019

View full text Add to dashboard Cite

The improved knowledge of pathogenetic mechanisms underlying lymphomagenesis and the discovery of the critical role of tumor microenvironments have enabled the design of new drugs against cell targets and pathways. The Food and Drug Administration (FDA) has approved several monoclonal antibodies (mAbs) and small molecule inhibitors (SMIs) for targeted therapy in hematology. This review focuses on the efficacy results of the currently available targeted agents and recaps the main ongoing trials in the setting of mature B-Cell non-Hodgkin lymphomas. The objective is to summarize the different classes of novel agents approved for mature B-cell lymphomas, to describe in synoptic tables the results they achieved and, finally, to draw future scenarios as we glimpse through the ongoing clinical trials. Characteristics and therapeutic efficacy are summarized for the currently approved mAbs [i.e., anti-Cluster of differentiation (CD) mAbs, immune checkpoint inhibitors, chimeric antigen receptor (CAR) T-cell therapy, and bispecific antibodies] as well as for SMIs i.e., inhibitors of B-cell receptor signaling, proteasome, mTOR BCL-2 HDAC pathways. The biological disease profiling of B-cell lymphoma subtypes may foster the discovery of innovative drug strategies for improving survival outcome in lymphoid neoplasms, as well as the trade-offs between efficacy and toxicity. The hope for clinical advantages should carefully be coupled with mindful awareness of the potential pitfalls and the occurrence of uneven, sometimes severe, toxicities.

show abstract

Targeting the ubiquitin-proteasome system for cancer treatment: discovering novel inhibitors from nature and drug repurposing

Cited by 92 publications

References 139 publications

Proteasome and Autophagy Pathway in Corneal Epithelial Cells with Limbal Stem Cell Deficiency

Proteasome and Autophagy Pathway in Corneal Epithelial Cells with Limbal Stem Cell Deficiency

RING finger protein 38 induces gastric cancer cell growth by decreasing the stability of the protein tyrosine phosphatase SHP‐1

Overview of Targeted Drugs for Mature B-Cell Non-hodgkin Lymphomas

Contact Info

Product

Resources

About