Related Experiment Video

Updated: Aug 26, 2025

Author Spotlight: A Selective Luciferase-Based Assay for Monitoring ATG4B 27 Activity in Cells
09:51

Author Spotlight: A Selective Luciferase-Based Assay for Monitoring ATG4B 27 Activity in Cells

Published on: June 30, 2023

996

Sirtuin 4 activates autophagy and inhibits tumorigenesis by upregulating the p53 signaling pathway

Juan Li1, Hanxiang Zhan2, Yidan Ren1

  • 1Department of Clinical Laboratory, The Second Hospital of Shandong University, 247 Beiyuan Street, Jinan, Shandong, 250033, China.

Cell Death and Differentiation
|October 8, 2022
PubMed

Insights

SIRT4 inhibits pancreatic cancer growth by activating autophagy. This pathway involves SIRT4 suppressing glutamine metabolism, leading to p53 phosphorylation and autophagy promotion, offering a potential therapeutic target for pancreatic ductal adenocarcinoma.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cellular Biology

Background:

  • Autophagy's role in cancer is complex and context-dependent.
  • Pancreatic ductal adenocarcinoma (PDAC) remains a significant health challenge with limited therapeutic options.

Purpose of the Study:

  • To identify regulators and mechanisms of autophagy in PDAC.
  • To investigate the role of sirtuin 4 (SIRT4) in PDAC progression and autophagy.

Main Methods:

  • In vitro cell culture experiments.
  • In vivo transgenic and xenografted animal models.
  • Analysis of human PDAC specimens.

Main Results:

  • SIRT4 was significantly associated with the autophagy pathway in PDAC.
  • SIRT4 inhibited tumor growth and promoted autophagy in PDAC models.
  • SIRT4 suppressed glutamine metabolism, activating p53 phosphorylation and inducing autophagy via the AMPKα pathway.
  • The SIRT4/AMPKα/p53/autophagy axis was clinically relevant in human PDAC.

Conclusions:

  • SIRT4-induced autophagy inhibits PDAC tumorigenesis and progression.
  • SIRT4 represents a potential therapeutic target for pancreatic cancer.

More Related Videos

Enhancement of Apoptotic and Autophagic Induction by a Novel Synthetic C-1 Analogue of 7-deoxypancratistatin in Human Breast Adenocarcinoma and Neuroblastoma Cells with Tamoxifen19:44

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

18.8K
Yeast As a Chassis for Developing Functional Assays to Study Human P5314:57

Yeast As a Chassis for Developing Functional Assays to Study Human P53

Published on: August 4, 2019

9.6K

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...
3.9K
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...
3.8K
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...
4.6K
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...
6.4K
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...
9.1K
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
4.9K