Related Experiment Video

Updated: May 28, 2026

Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo
08:19

Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo

Published on: July 20, 2019

S-Nitrosylation of mitogen activated protein kinase phosphatase-1 suppresses radiation-induced apoptosis

Weiping Guan1, Jibin Sha, Xiaojuan Chen

  • 1Nanlou Department of Neurology, Chinese PLA General Hospital, Beijing, PR China.

Cancer Letters
|October 22, 2011
PubMed

Insights

Mitogen activated protein kinase phosphatase-1 (MKP-1) protein stability and activity are enhanced by S-nitrosylation, leading to radio-resistance in head and neck cancer (HNC). This discovery offers a new target for improving HNC radiotherapy efficacy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Radiotherapy is a primary treatment for head and neck cancer (HNC).
  • Elevated Mitogen activated protein kinase phosphatase-1 (MKP-1) levels in tumors correlate with reduced radiotherapy efficacy.
  • Mechanisms for HNC radiosensitivity and increased MKP-1 remain unclear.

Purpose of the Study:

  • Investigate the role of MKP-1 in HNC radio-resistance.
  • Elucidate the mechanisms behind increased MKP-1 levels in HNC.
  • Identify potential therapeutic targets to enhance HNC radiotherapy.

Main Methods:

  • Utilized S-nitrosylation assays to examine MKP-1 modification.
  • Assessed MKP-1 protein stability and phosphatase activity.
  • Employed co-culture systems with transfected HNC cells and activated macrophages to mimic the tumor microenvironment.

Main Results:

  • S-nitrosylation of MKP-1 at Cysteine 258 enhances its stability and phosphatase activity.
  • Increased MKP-1 activity promotes an anti-apoptotic effect, contributing to HNC radio-resistance.
  • The tumor microenvironment, specifically activated macrophages, influences MKP-1 S-nitrosylation and HNC radiosensitivity.

Conclusions:

  • S-nitrosylation of MKP-1 is a novel mechanism driving radio-resistance in head and neck cancer.
  • Targeting MKP-1 S-nitrosylation could represent a new strategy to improve HNC radiotherapy outcomes.
  • Understanding the tumor microenvironment's role in MKP-1 regulation is crucial for developing effective cancer therapies.

More Related Videos

Assessment of Mitochondrial Functions and Cell Viability in Renal Cells Overexpressing Protein Kinase C Isozymes15:43

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

Published on: January 7, 2013

Related Concept Videos

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...
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...
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...
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...
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...
NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...