Bortezomib decreases Rb phosphorylation and induces caspase-dependent apoptosis in Imatinib-sensitive and -resistant Bcr-Abl1-expressing cells

Albero, M. Pilar; Vaquer, J M; Andreu, Enrique J.; Villanueva, Jacylyn; Franch, L; Ivorra, Carmen; Poch, Enric; Agirre, Xabier; Prósper, Felipe; Pérez‐Roger, Ignacio

doi:10.1038/onc.2010.81

Cited by 22 publications

(29 citation statements)

References 42 publications

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“…However, this effect was only transient and perhaps does not explain the cellular effects of Bortezomib. In contrast, in Baf/3-derived cell lines exogenously expressing Bcr-Abl, there was no effect of Bortezomib on NF-κB activity (Albero et al, 2010). However, in this same study, the non-canonical NF-κB pathway was analyzed and the results show that Bortezomib prevents the activation of NF-κB2.…”

Section: Molecular Changes In CML Cells Treated With Bortezomibmentioning

confidence: 65%

“…Moreover, exogenous p27 kip1 expression partially antagonizes the effect of Bcr-Abl on proliferation (Albero et al, 2010;Andreu et al, 2005;Bretones et al, 2011;Jonuleit et al, 2000). By inhibiting the tyrosine kinase activity of BcrAbl with Imatinib, the half-life of p27 kip1 is increased, meaning that Bcr-Abl induces the degradation of p27 kip1 .…”

Section: Bcr-abl and The Proteasomementioning

confidence: 99%

“…Proteasome inhibition with Bortezomib in Bcr-Abl expressing cell models or primary CD34+ cells from CML patients results in a cell cycle inhibition and induction of apoptosis (Albero et al, 2010;Gatto et al, 2003;Jagani et al, 2009). Different key regulators are affected by Bortezomib leading to the detection of apoptosis markers, such as the activation (cleavage) of caspases (3, 8 and 9), or the down-regulation of Bcl-x L and induction of Bim.…”

Section: Molecular Changes In CML Cells Treated With Bortezomibmentioning

confidence: 99%

“…Among these key events, Bortezomib treatment reverses the Bcr-Abl suppression of FoxO proteins and blocks the activation of NF-κB. Although apoptosis induction is a commonplace of Bortezomib treatment, the inhibition of the cell cycle can be at the G1/S transition or at the G2/M boundary, depending on the cell models used (Albero et al, 2010;Gatto et al, 2003). The cell cycle inhibition at the G1/S transition can be explained by the accumulation of p27 kip1 in Bortezomib treated cells (Fig.…”

Section: Molecular Changes In CML Cells Treated With Bortezomibmentioning

confidence: 99%

“…The dephosphorylation of Rb is followed by its caspase-dependent processing and degradation, something associated with the induction of apoptosis. As a consequence of the impact on Rb phosphorylation, Bortezomib treatment also results in the down-regulation of cyclin A expression (Albero et al, 2010). In cell lines derived from CML patients in blast crisis, Bortezomib induces the accumulation of IκB , correlating with a decrease in the NF-κB DNA binding activity in the nucleus at the same time (Gatto et al, 2003).…”

Section: Molecular Changes In CML Cells Treated With Bortezomibmentioning

confidence: 99%

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The Proteasome as a Therapeutic Target in Chronic Myeloid Leukemia

Pérez‐Roger¹,

Albero²

2011

Myeloid Leukemia - Basic Mechanisms of Leukemogenesis

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Section: Molecular Changes In CML Cells Treated With Bortezomibmentioning

confidence: 65%

Section: Bcr-abl and The Proteasomementioning

confidence: 99%

Section: Molecular Changes In CML Cells Treated With Bortezomibmentioning

confidence: 99%

Section: Molecular Changes In CML Cells Treated With Bortezomibmentioning

confidence: 99%

Section: Molecular Changes In CML Cells Treated With Bortezomibmentioning

confidence: 99%

See 3 more Smart Citations

The Proteasome as a Therapeutic Target in Chronic Myeloid Leukemia

Pérez‐Roger¹,

Albero²

2011

Myeloid Leukemia - Basic Mechanisms of Leukemogenesis

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Metal-based proteasomal deubiquitinase inhibitors as potential anticancer agents

Chen

Yang

Xiao

et al. 2017

Cancer Metastasis Rev

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Deubiquitinases (DUBs) play an important role in protein quality control in eukaryotic cells due to their ability to specifically remove ubiquitin from substrate proteins. Therefore, recent findings have focused on the relevance of DUBs to cancer development, and pharmacological intervention on these enzymes has become a promising strategy for cancer therapy. In particular, several DUBs are physically and/or functionally associated with the proteasome and are attractive targets for the development of novel anticancer drugs. The successful clinical application of cisplatin in cancer treatment has prompted researchers to develop various metal-based anticancer agents with new properties. Recently, we have reported that several metal-based drugs, such as the antirheumatic gold agent auranofin (AF), the antifouling paint biocides copper pyrithione (CuPT) and zinc pyrithione (ZnPT), and also our two synthesized complexes platinum pyrithione (PtPT) and nickel pyrithione (NiPT), can target the proteasomal DUBs UCHL5 and USP14. In this review, we summarize the recently reported small molecule inhibitors of proteasomal DUBs, with a focus on discussion of the unique nature of metal-based proteasomal DUB inhibitors and their anticancer activity.

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