Relationship between inhibition of protein methylase I and inhibition of Rous sarcoma virus-induced cell

Cancer Research
|November 1, 1979
PubMed

Insights

Structural analogs of S-adenosylhomocysteine effectively inhibit protein methylase I and virus-induced cell transformation. This study establishes a structure-activity relationship for protein methylase I inhibition.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Virology

Background:

  • Virus-induced cell transformation is a complex process.
  • Protein methylase I plays a role in cellular processes.
  • S-adenosylhomocysteine analogs are being investigated for biological activity.

Purpose of the Study:

  • To investigate the correlation between protein methylase I inhibition and virus-induced cell transformation.
  • To establish a structure-activity relationship for protein methylase I inhibitors.

Main Methods:

  • Synthesis and testing of structural analogs of S-adenosylhomocysteine.
  • Enzyme inhibition assays for protein methylase I.
  • Cell transformation assays using Rous sarcoma virus-induced chick embryo fibroblasts.

Main Results:

  • A strong correlation was observed between the inhibition of protein methylase I and the inhibition of virus-induced cell transformation.
  • Effective inhibitors of protein methylase I were also effective inhibitors of Rous sarcoma virus-induced chick embryo fibroblast transformation.
  • Inhibitory effects were consistent across normal and transformed cells, with no significant variation in inhibition constants after enzyme purification.

Conclusions:

  • Structural analogs of S-adenosylhomocysteine are potent inhibitors of both protein methylase I and virus-induced cell transformation.
  • A clear structure-activity relationship for protein methylase I inhibition can be established based on kinetic data.
  • These findings suggest protein methylase I as a potential therapeutic target for viral infections and cancer.

Related Concept Videos

MicroRNAs01:22

MicroRNAs

MicroRNA (miRNA) are short, regulatory RNA transcribed from introns—non-coding regions of a gene—or intergenic regions—stretches of DNA present between genes. Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA ends...
Experimental RNAi02:15

Experimental RNAi

RNA interference (RNAi) is a cellular mechanism that inhibits gene expression by suppressing its transcription or activating the RNA degradation process. The mechanism was discovered by Andrew Fire and Craig Mello in 1998 in plants. Today, it is observed in almost all eukaryotes, including protozoa, flies, nematodes, insects, parasites, and mammals. This precise cellular mechanism of gene silencing has been developed into a technique that provides an efficient way to identify and determine the...
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...
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...
Rous Sarcoma Virus (RSV) and Cancer01:03

Rous Sarcoma Virus (RSV) and Cancer

Rous Sarcoma virus or RSV was discovered by F. Peyton Rous in the year 1911 as a filterable transmissible agent that could cause tumors in chickens. He won a Nobel Prize for this discovery in 1966. His experiments clearly demonstrated that some cancers could be caused by infectious agents and led to the discovery of many more cancer-causing viruses in animals as well as humans.
RSV is a retrovirus that contains two copies of a plus-strand  RNA genome. Its genome consists of four main open...
MicroRNAs01:22

MicroRNAs

MicroRNA (miRNA) are short, regulatory RNA transcribed from introns (non-coding regions of a gene) or intergenic regions (stretches of DNA present between genes). Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself, forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA...