Related Experiment Video

Updated: Apr 13, 2026

Assessing Cellular Target Engagement by SHP2 PTPN11 Phosphatase Inhibitors
08:45

Assessing Cellular Target Engagement by SHP2 PTPN11 Phosphatase Inhibitors

Published on: July 17, 2020

6.8K

Dysregulation of AKT Pathway by SMYD2-Mediated Lysine Methylation on PTEN

Makoto Nakakido1, Zhenzhong Deng1, Takehiro Suzuki2

  • 1Section of Hematology/Oncology, Department of Medicine, The University of Chicago, Chicago, IL, USA.

Neoplasia (New York, N.Y.)
|May 1, 2015
PubMed

Insights

Researchers discovered that the SMYD2 protein methylates PTEN, a tumor suppressor. This methylation activates the AKT pathway, promoting cancer cell growth and revealing a new mechanism for PTEN regulation in cancer.

Area of Science:

  • Molecular Biology
  • Oncology
  • Biochemistry

Background:

  • PTEN is a tumor suppressor protein regulating the PI3K-AKT pathway.
  • PTEN's function is modulated by various posttranslational modifications.
  • PTEN methylation has not been previously reported.

Purpose of the Study:

  • To investigate the role of protein methylation in PTEN regulation.
  • To identify specific methyltransferases that modify PTEN.
  • To elucidate the functional consequences of PTEN methylation in cancer.

Main Methods:

  • In vitro and in vivo methylation assays using SMYD2 and PTEN.
  • Knockdown of SMYD2 in breast cancer cell lines.
  • Analysis of AKT phosphorylation levels.
  • Site-directed mutagenesis of PTEN (K313A) and assessment of downstream signaling.

Main Results:

  • SMYD2 was identified as a PTEN methyltransferase, specifically methylating PTEN at lysine 313.
  • SMYD2 knockdown inhibited breast cancer cell growth and reduced AKT phosphorylation.
  • Mutation of PTEN at lysine 313 prevented PTEN phosphorylation at serine 380, a known inactivation event.
  • SMYD2-mediated PTEN methylation negatively regulates PTEN's tumor suppressor activity.

Conclusions:

  • Lysine methylation by SMYD2 is a novel mechanism for PTEN dysregulation in human cancer.
  • SMYD2-mediated methylation of PTEN promotes cancer progression by activating the PI3K-AKT pathway.
  • Targeting SMYD2 may offer a therapeutic strategy for cancers with PTEN alterations.

More Related Videos

Specificity Analysis of Protein Lysine Methyltransferases Using SPOT Peptide Arrays08:48

Specificity Analysis of Protein Lysine Methyltransferases Using SPOT Peptide Arrays

Published on: November 29, 2014

14.6K
Author Spotlight: Exploring the Role of Inflammation in the Co-occurrence of Primary Sjogren's Syndrome and Lung Adenocarcinoma10:21

Author Spotlight: Exploring the Role of Inflammation in the Co-occurrence of Primary Sjogren's Syndrome and Lung Adenocarcinoma

Published on: September 20, 2024

957

Related Concept Videos

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...
6.5K
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...
5.4K
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...
5.1K
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...
14.1K
Covalently Linked Protein Regulators02:04

Covalently Linked Protein Regulators

Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein....
9.9K
Epigenetic Regulation01:37

Epigenetic Regulation

Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
4.3K