Related Experiment Video

Updated: Jun 20, 2026

Enhancement of Apoptotic and Autophagic Induction by a Novel Synthetic C-1 Analogue of 7-deoxypancratistatin in Human Breast Adenocarcinoma and Neuroblastoma Cells with Tamoxifen
19:44

Enhancement of Apoptotic and Autophagic Induction by a Novel Synthetic C-1 Analogue of 7-deoxypancratistatin in Human Breast Adenocarcinoma and Neuroblastoma Cells with Tamoxifen

Published on: May 30, 2012

Androgen via p21 inhibits tumor necrosis factor alpha-induced JNK activation and apoptosis

Fangming Tang1, John Kokontis, Yuting Lin

  • 1Ben May Department for Cancer Research, University of Chicago, Chicago, Illinois 60637, USA.

The Journal of Biological Chemistry
|September 3, 2009
PubMed

Insights

Androgens promote tissue survival by inhibiting JNK activation and apoptosis through a mechanism involving the androgen receptor (AR) and p21. This pathway highlights a novel cross-talk essential for androgen

Area of Science:

  • Molecular Biology
  • Endocrinology
  • Cell Signaling

Background:

  • Androgens are crucial male hormones that support the growth and survival of target tissues.
  • The precise molecular mechanisms by which androgens exert their survival functions remain incompletely understood.
  • Tumor necrosis factor alpha (TNF-α) can induce JNK activation and apoptosis, processes that may be counteracted by survival factors.

Purpose of the Study:

  • To elucidate the molecular mechanism by which androgens mediate their survival function in target tissues.
  • To investigate the role of p21 in mediating the anti-apoptotic effects of androgens.
  • To explore the potential cross-talk between androgen signaling and the JNK pathway.

Main Methods:

  • Investigated androgen's effect on TNF-α-induced JNK activation and apoptosis in relevant cellular models.
  • Assessed the requirement for androgen receptor (AR) transcriptional activity and de novo protein synthesis.
  • Utilized genetic manipulation, including the interruption of p21 alleles, to confirm its role in androgen's inhibitory effects.

Main Results:

  • Androgen was found to inhibit TNF-α-induced JNK activation and apoptosis.
  • This inhibition is dependent on the transcriptional activity of the androgen receptor (AR) and requires new protein synthesis.
  • Androgen receptor (AR) induces the expression of p21, which mediates the inhibition of JNK signaling and apoptosis.
  • Genetic disruption of p21 abrogated the inhibitory effects of androgen, confirming p21's critical role.

Conclusions:

  • Androgen exerts a survival function by inhibiting JNK activation and apoptosis via the induction of p21.
  • This pathway involves a novel cross-talk between androgen receptor (AR) signaling and the JNK pathway.
  • The findings provide a detailed molecular mechanism underlying androgen's role in tissue survival.

More Related Videos

Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway07:15

Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway

Published on: August 23, 2024

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...
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...
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...
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
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...
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...