Related Experiment Video

Updated: Dec 5, 2025

Fully Processed Recombinant KRAS4b: Isolating and Characterizing the Farnesylated and Methylated Protein
07:08

Fully Processed Recombinant KRAS4b: Isolating and Characterizing the Farnesylated and Methylated Protein

Published on: January 16, 2020

6.0K

KRAS K104 modification affects the KRASG12D-GEF interaction and mediates cell growth and motility

Chih-Chieh Chen1,2, Chia-Yi Hsu3, Hsiao-Yun Lin3

  • 1Institute of Medical Science and Technology, National Sun Yat-sen University, Kaohsiung, 80424, Taiwan.

Scientific Reports
|October 16, 2020
PubMed

Insights

KRAS G12D K104Q modification hinders Guanine nucleotide Exchange Factor (GEF) binding, reducing tumor cell growth and invasion. This suggests targeting KRAS Lysine 104 offers a new therapeutic strategy for cancers.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Mutant RAS genes are crucial in tumor development.
  • Lysine residue 104 (K104) is implicated in regulating RAS function.
  • The specific role of KRAS K104 modification in KRAS G12D mutants requires elucidation.

Purpose of the Study:

  • To investigate the impact of KRAS K104 modification on KRAS G12D structure and function.
  • To analyze the binding interactions between modified KRAS G12D and Guanine nucleotide Exchange Factor (GEF).
  • To explore the therapeutic potential of targeting KRAS K104.

Main Methods:

  • Computational simulation of KRAS G12D protein structures with K104 modifications (K104A, K104Q).
  • Determination of molecular trajectories and binding free energy with GEF.
  • Experimental validation including cell growth, invasion, migration assays, and whole-genome cDNA microarray analysis.

Main Results:

  • KRAS G12D/K104Q induced structural changes in alpha helices, increasing KRAS instability and hindering GEF binding by 6.14 kJ/mol.
  • KRAS G12D/K104Q reduced binding to Raf1 RBD, consequently decreasing cancer cell growth, invasion, and migration.
  • Whole-genome analysis revealed decreased expression of NPIPA2, DUSP1, and IL6 in lung and ovarian cancer cells with KRAS G12D/K104Q.

Conclusions:

  • KRAS K104 modification significantly impacts KRAS G12D stability and GEF interaction.
  • Targeting KRAS K104 presents a potential therapeutic avenue for KRAS-driven cancers.
  • Further research into KRAS K104 modifications could lead to novel cancer treatments.

More Related Videos

Impedance-based Real-time Measurement of Cancer Cell Migration and Invasion09:23

Impedance-based Real-time Measurement of Cancer Cell Migration and Invasion

Published on: April 2, 2020

6.8K
Real-Time Quantitative Measurement of Tumor Cell Migration and Invasion Following Synthetic mRNA Transfection11:00

Real-Time Quantitative Measurement of Tumor Cell Migration and Invasion Following Synthetic mRNA Transfection

Published on: June 23, 2023

2.0K

Related Concept Videos

The Ras Gene02:38

The Ras Gene

The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a...
6.8K
Small GTPases - Ras and Rho01:24

Small GTPases - Ras and Rho

Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:
4.9K
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...
5.0K
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...
4.4K
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...
4.9K
GPCRs Regulate Adenylyl Cylase Activity01:09

GPCRs Regulate Adenylyl Cylase Activity

Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of...
6.6K