Related Experiment Video

Updated: Jun 12, 2026

Assessment of Mitochondrial Functions and Cell Viability in Renal Cells Overexpressing Protein Kinase C Isozymes
15:43

Assessment of Mitochondrial Functions and Cell Viability in Renal Cells Overexpressing Protein Kinase C Isozymes

Published on: January 7, 2013

Regulation of prostate cancer cell survival by protein kinase Cepsilon involves bad phosphorylation and modulation of

John Meshki1, M Cecilia Caino, Vivian A von Burstin

  • 1Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6160, USA.

The Journal of Biological Chemistry
|June 23, 2010
PubMed

Insights

Protein kinase Cepsilon (PKCepsilon) promotes prostate cancer cell survival by inhibiting apoptosis. Inhibiting PKCepsilon enhances cancer cell death, revealing its role in tumor progression.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Signaling

Background:

  • Protein kinase Cepsilon (PKCepsilon) is overexpressed in human tumors, including prostate cancer.
  • Its role in prostate cancer cell apoptosis is currently unknown.
  • Prostate cancer cells undergo apoptosis via PKCdelta upon phorbol ester stimulation.

Purpose of the Study:

  • To investigate the role of PKCepsilon in prostate cancer cell apoptosis.
  • To elucidate the mechanisms by which PKCepsilon influences cell survival and death pathways.
  • To determine if PKCepsilon modulates the response to apoptotic stimuli like TNFalpha.

Main Methods:

  • RNA interference (RNAi) to deplete PKCepsilon.
  • Expression of a dominant-negative kinase-dead PKCepsilon mutant.
  • Adenoviral overexpression of PKCepsilon.
  • Analysis of apoptosis, TNFalpha release, JNK activation, and Bad phosphorylation.
  • In vitro kinase assays and subcellular localization studies.

Main Results:

  • PKCepsilon depletion potentiated apoptosis induced by phorbol ester (PMA) and sensitized cells to TNFalpha.
  • PKCepsilon overexpression protected cells against apoptotic stimuli.
  • PKCepsilon depletion enhanced PMA-induced TNFalpha release and JNK activation.
  • PKCepsilon promoted phosphorylation of Bad at Ser(112) independently of Akt, ERK, or p90Rsk.
  • PKCepsilon localized to mitochondria and phosphorylated Bad in vitro.

Conclusions:

  • PKCepsilon modulates survival in prostate cancer cells through multiple pathways.
  • PKCepsilon plays a pro-survival role by inhibiting apoptosis and promoting Bad phosphorylation.
  • Targeting PKCepsilon may represent a therapeutic strategy for prostate cancer.

More Related Videos

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants07:38

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants

Published on: June 6, 2025

Related Concept Videos

mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...
Amplifying Signals via Enzymatic Cascade01:22

Amplifying Signals via Enzymatic Cascade

When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze the...