Related Experiment Video

Updated: Aug 22, 2026

Measuring Caspase Activity Using a Fluorometric Assay or Flow Cytometry
05:29

Measuring Caspase Activity Using a Fluorometric Assay or Flow Cytometry

Published on: March 24, 2023

Protein kinase Cdelta regulates apoptosis via activation of STAT1

Tracie A DeVries1, Rachelle L Kalkofen, Angela A Matassa

  • 1Department of Craniofacial Biology, School of Dentistry, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA.

The Journal of Biological Chemistry
|August 24, 2004
PubMed

Insights

Protein kinase Cdelta (PKCdelta) activation triggers STAT1 activation, a key step in DNA damage-induced apoptosis. This study identifies STAT1 as a crucial downstream target of PKCdelta in the apoptotic pathway.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Protein kinase Cdelta (PKCdelta) plays a role in programmed cell death.
  • The downstream signaling pathways regulated by PKCdelta during apoptosis are not well understood.

Purpose of the Study:

  • To investigate the downstream effectors of PKCdelta in apoptotic cells.
  • To determine if STAT1 is a downstream target of PKCdelta in the context of DNA damage-induced apoptosis.

Main Methods:

  • Utilized HeLa and U3A STAT1-deficient cells.
  • Treated cells with etoposide to induce DNA damage.
  • Assessed STAT1 phosphorylation, STAT1-PKCdelta association, and reporter gene transcription.
  • Investigated the role of nuclear localization for both proteins in apoptosis.

Main Results:

  • Etoposide treatment induced STAT1 phosphorylation at Ser(727) and its association with PKCdelta.
  • PKCdelta inhibition or depletion blocked STAT1 activation and transcription.
  • PKCdelta-mediated apoptosis was suppressed in STAT1-deficient cells but restored by STAT1 re-expression.
  • Nuclear translocation of both PKCdelta and STAT1 was essential for apoptosis induction.

Conclusions:

  • STAT1 is a downstream target of PKCdelta in DNA damage-induced apoptosis.
  • PKCdelta may mediate apoptosis by activating STAT1 and its target genes.
  • Nuclear localization of PKCdelta and STAT1 is critical for initiating the apoptotic cascade.

More Related Videos

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death09:18

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death

Published on: December 27, 2016

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries08:49

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries

Published on: January 22, 2019

Related Concept Videos

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...
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...
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
Caspases01:24

Caspases

Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside cells.