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Article

Bcl10 crucially nucleates the pro-apoptotic complexes comprising PDK1, PKCζ and caspase-3 at the nuclear envelope of etoposide-treated human cervical carcinoma C4-I cells

  • Authors:
    • Anna Chiarini
    • Daisong Liu
    • Ubaldo Armato
    • Ilaria Dal Prà
  • View Affiliations / Copyright

    Affiliations: Histology and Embryology Section, Department of Life and Reproduction Sciences, University of Verona Medical School, I‑37134 Verona, Venetia, Italy, Chongqing Key Laboratory for Disease Proteomics, Institute of Burn Research, Southwest Hospital, Third Military Medical University, Chongqing 400038, P.R. China
  • Pages: 845-856
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    Published online on: July 20, 2015
       https://doi.org/10.3892/ijmm.2015.2290
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Abstract

Protein kinase (PK)Cζ signaling at various subcellular levels affects cell survival, differentiation, growth and/or apoptosis. However, the mechanisms modulating PKCζ activity at the nuclear membrane (NM) are not yet fully understood. Previously, we demonstrated that PKCζ interacts with the B‑cell lymphoma 10 (Bcl10) protein at the NM of human cervical carcinoma (HCC) C4‑I cells. In the present study, we aimed to further clarify the interactions between PKCζ, Bcl10 and other proteins co-immunoprecipitated from NMs isolated from untreated and etoposide (also known as VP‑16; 2.0 µg/ml)‑treated C4‑I cells using biochemical and proteomics analyses. Aside from the Bcl10 protein, 3‑phosphoinositide‑dependent protein kinase‑1 (PDK1) also co-immunoprecipitated with PKCζ from NMs of C4‑I cells, indicating the assembly of a heterotrimeric complex, which increased with time in VP‑16‑exposed cells, as did the activity of PDK1‑phosphorylated‑PKCζ. In turn, PKCζ‑phosphorylated‑Bcl10 straddled an enlarged complex which comprised caspase‑3. Subsequently, activity‑enhanced caspase‑3 cleaved and inactivated PKCζ. Finally, the suppression of Bcl10 using specific siRNA or lentiviral transduction prevented the increase in the PDK1•PKCζ association, the increase in the activity of PKCζ and caspase‑3, as well as the caspase‑3‑mediated PKCζ proteolysis and inactivation from occurring at the NMs of the VP‑16‑exposed C4‑I cells. Our observations provide evidence that Bcl10 acts as a pivotal pro-apoptotic protein which crucially nucleates complexes comprising PDK1, PKCζ and active caspase‑3 at the NMs of VP‑16‑exposed C4‑I cells. Hence, our data suggest that Bcl10 and PKCζ are potential therapeutic targets in the treatment of HCC.
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Copy and paste a formatted citation
Spandidos Publications style
Chiarini A, Liu D, Armato U and Dal Prà I: Bcl10 crucially nucleates the pro-apoptotic complexes comprising PDK1, PKCζ and caspase-3 at the nuclear envelope of etoposide-treated human cervical carcinoma C4-I cells. Int J Mol Med 36: 845-856, 2015.
APA
Chiarini, A., Liu, D., Armato, U., & Dal Prà, I. (2015). Bcl10 crucially nucleates the pro-apoptotic complexes comprising PDK1, PKCζ and caspase-3 at the nuclear envelope of etoposide-treated human cervical carcinoma C4-I cells. International Journal of Molecular Medicine, 36, 845-856. https://doi.org/10.3892/ijmm.2015.2290
MLA
Chiarini, A., Liu, D., Armato, U., Dal Prà, I."Bcl10 crucially nucleates the pro-apoptotic complexes comprising PDK1, PKCζ and caspase-3 at the nuclear envelope of etoposide-treated human cervical carcinoma C4-I cells". International Journal of Molecular Medicine 36.3 (2015): 845-856.
Chicago
Chiarini, A., Liu, D., Armato, U., Dal Prà, I."Bcl10 crucially nucleates the pro-apoptotic complexes comprising PDK1, PKCζ and caspase-3 at the nuclear envelope of etoposide-treated human cervical carcinoma C4-I cells". International Journal of Molecular Medicine 36, no. 3 (2015): 845-856. https://doi.org/10.3892/ijmm.2015.2290
Copy and paste a formatted citation
x
Spandidos Publications style
Chiarini A, Liu D, Armato U and Dal Prà I: Bcl10 crucially nucleates the pro-apoptotic complexes comprising PDK1, PKCζ and caspase-3 at the nuclear envelope of etoposide-treated human cervical carcinoma C4-I cells. Int J Mol Med 36: 845-856, 2015.
APA
Chiarini, A., Liu, D., Armato, U., & Dal Prà, I. (2015). Bcl10 crucially nucleates the pro-apoptotic complexes comprising PDK1, PKCζ and caspase-3 at the nuclear envelope of etoposide-treated human cervical carcinoma C4-I cells. International Journal of Molecular Medicine, 36, 845-856. https://doi.org/10.3892/ijmm.2015.2290
MLA
Chiarini, A., Liu, D., Armato, U., Dal Prà, I."Bcl10 crucially nucleates the pro-apoptotic complexes comprising PDK1, PKCζ and caspase-3 at the nuclear envelope of etoposide-treated human cervical carcinoma C4-I cells". International Journal of Molecular Medicine 36.3 (2015): 845-856.
Chicago
Chiarini, A., Liu, D., Armato, U., Dal Prà, I."Bcl10 crucially nucleates the pro-apoptotic complexes comprising PDK1, PKCζ and caspase-3 at the nuclear envelope of etoposide-treated human cervical carcinoma C4-I cells". International Journal of Molecular Medicine 36, no. 3 (2015): 845-856. https://doi.org/10.3892/ijmm.2015.2290
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