Prostate Apoptosis Response 4 (Par-4), a Novel Substrate of Caspase-3 during Apoptosis Activation

Chaudhry, Parvesh; Singh, Mohan; Parent, Stefan; Asselin, Éric

doi:10.1128/mcb.06321-11

Cited by 67 publications

(73 citation statements)

References 41 publications

(47 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the present manuscript, we focused on the ~25kDa cleaved form of Par-4 which has been previously reported as a product of Par-4 following its cleavage by caspase-8 and caspase-3 under apoptotic stimuli [14, 37]. We found that in ovarian and endometrial cancer cells, cl-Par-4 undergoes rapid degradation by the proteasome in baseline conditions but is stabilized upon cisplatin treatment.…”

Section: Discussionmentioning

confidence: 86%

“…We have previously demonstrated that upon cisplatin treatment, Par-4 is cleaved by caspase-3 at D132 and subsequently generates a 25kDa fragment, probed with Par-4 antibody, that we named cl-Par-4 (Figure 1A) [14]. We hence decided to evaluate if the same effect would be observed in different ovarian (A2780, A2780CP) and endometrial (Ishikawa, Hec-1a) cancer cells.…”

Section: Resultsmentioning

confidence: 99%

“…We also recently discovered that Par-4 is cleaved by caspase-3 at D131 during apoptosis in many different cancer cells. This cleavage consistently generates a 25kDa cleaved fragment (cl-Par-4) that contains the nuclear localization sequence (NLS2), the selective for apoptosis induction in cancer cells domain (SAC) and the leucine zipper domains [14]. Most importantly, the accumulation of cl-Par-4 under various apoptotic stimuli seems to be an important factor related to the chemosensitivity of cancer cells and the level of apoptosis observed.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Post-translational regulation of the cleaved fragment of Par-4 in ovarian and endometrial cancer cells

et al. 2016

Self Cite

View full text Add to dashboard Cite

We recently reported the caspase3-dependent cleavage of Par-4 resulting in the accumulation of a 25kDa cleaved-Par-4 (cl-Par-4) fragment and we investigated in the present study the mechanisms regulating this fragment using cl-Par-4-expressing stable clones derived from ovarian and endometrial cancer cell lines.Cl-Par-4 protein was weakly express in all stable clones despite constitutive expression. However, upon cisplatin treatment, cl-Par-4 levels increased up to 50-fold relative to baseline conditions. Treatment of stable clones with proteasome and translation inhibitors revealed that cisplatin exposure might in fact protect cl-Par-4 from proteasome-dependent degradation. PI3K and MAPK pathways were also implicated as evidenced by an increase of cl-Par-4 in the presence of PI3K inhibitors and a decrease using MAPK inhibitors. Finally using bioinformatics resources, we found diverse datasets showing similar results to those we observed with the proteasome and cl-Par-4 further supporting our data.These new findings add to the complex mechanisms regulating Par-4 expression and activity, and justify further studies addressing the biological significance of this phenomenon in gynaecological cancer cells.

show abstract

Section: Discussionmentioning

confidence: 86%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Post-translational regulation of the cleaved fragment of Par-4 in ovarian and endometrial cancer cells

et al. 2016

Self Cite

View full text Add to dashboard Cite

show abstract

“…Par-4 is also known to be cleaved by caspase-3 and decreased protein levels were thought to be attributed to loss of the full protein. 41 Surprisingly there was no increase in levels of cleaved Par-4 during treatment with WA (data not shown) but a significant decrease, which was not altered by inclusion of Z-VAD FMK, a pan-caspase inhibitor (Fig. S2, and data not shown).…”

Section: Discussionmentioning

confidence: 87%

Anti-cancer activity of withaferin A in B-cell lymphoma

McKenna

Gachuki

Alhakeem

et al. 2015

Cancer Biology & Therapy

View full text Add to dashboard Cite

Abbreviations: WA, Withaferin A; DLBCL, Diffuse large B cell lymphoma.Withaferin A (WA), a withanolide from the plant, Ashwagandha (Withania somnifera) used in Ayurvedic medicine, has been found to be valuable in the treatment of several medical ailments. WA has been found to have anticancer activity against various solid tumors, but its effects on hematological malignancies have not been studied in detail. WA strongly inhibited the survival of several human and murine B cell lymphoma cell lines. Additionally, in vivo studies with syngeneic-graft lymphoma cells suggest that WA inhibits the growth of tumor but does not affect other proliferative tissues. We demonstrate that WA inhibits the efficiency of NF-kB nuclear translocation in diffuse large B cell lymphomas and found that WA treatment resulted in a significant decrease in protein levels involved in B cell receptor signaling and cell cycle regulation. WA inhibited the activity of heat shock protein (Hsp) 90 as reflected by a sharp increase in Hsp70 expression levels. Hence, we propose that the anti-cancer effects of WA in lymphomas are likely due to its ability to inhibit Hsp90 function and subsequent reduction of critical kinases and cell cycle regulators that are clients of Hsp90.

show abstract

“…Determination of Apoptosis Level-The induction of apoptosis was determined by counting the apoptotic cells (irregular Hoechst nuclear staining with multiple bright specks of chromatin fragmentation and condensation) stained with Hoechst 33258 dye (Sigma) and by flow cytometer analysis of annexin V/propidium iodide staining as described previously (36).…”

Section: Methodsmentioning

confidence: 99%

Keratin 8 and 18 Loss in Epithelial Cancer Cells Increases Collective Cell Migration and Cisplatin Sensitivity through Claudin1 Up-regulation

Fortier

Asselin

Cadrin

2013

Journal of Biological Chemistry

Self Cite

190

141

View full text Add to dashboard Cite

Background: Loss of keratins 8 and 18 (K8/18) is a hallmark of epithelial-mesenchymal transition (EMT), but its role in tumor progression is unclear. Results: Epithelial cancer cells depleted in K8/18 are more invasive and sensitive to cisplatin through the up-regulation of claudin1. Conclusion: K8/18 loss promotes collective cancer cell migration without inducing EMT. Significance: Cancer cell invasion can arise from K8/18 loss independently of EMT.

show abstract

Prostate Apoptosis Response 4 (Par-4), a Novel Substrate of Caspase-3 during Apoptosis Activation

Cited by 67 publications

References 41 publications

Post-translational regulation of the cleaved fragment of Par-4 in ovarian and endometrial cancer cells

Post-translational regulation of the cleaved fragment of Par-4 in ovarian and endometrial cancer cells

Anti-cancer activity of withaferin A in B-cell lymphoma

Keratin 8 and 18 Loss in Epithelial Cancer Cells Increases Collective Cell Migration and Cisplatin Sensitivity through Claudin1 Up-regulation

Contact Info

Product

Resources

About