Related Experiment Video
Updated: Jun 20, 2026
14:28
Peptide-based Identification of Functional Motifs and their Binding Partners
Published on: June 30, 2013
Identification of a novel, widespread, and functionally important PCNA-binding motif
Karin M Gilljam1, Emadoldin Feyzi, Per A Aas
1Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology, N-7489 Trondheim, Norway.
The Journal of Cell Biology
|September 9, 2009
Summary
Researchers discovered a new protein interaction motif, APIM, crucial for DNA repair and cell cycle control. This motif mediates interactions with PCNA, a key player in DNA replication and repair, especially under genotoxic stress.
Area of Science:
- Molecular Biology
- Cell Biology
- Biochemistry
Background:
- Proliferating cell nuclear antigen (PCNA) is vital for DNA replication and interacts with numerous proteins via the PIP box motif.
- The oxidative demethylase human AlkB homologue 2 (hABH2) has been observed to colocalize with PCNA in replication foci.
Purpose of the Study:
- To identify and characterize novel PCNA-interacting motifs beyond the known PIP box.
- To investigate the role of these new motifs in DNA maintenance, transcription, and cell cycle regulation.
Main Methods:
- Bioinformatic identification of the AlkB homologue 2 PCNA-interacting motif (APIM) in protein databases.
- Experimental verification of functional APIM in selected proteins.
- Cellular sensitivity assays upon expression of APIM peptides.
Main Results:
- A novel PCNA-interacting motif, termed APIM, was identified in hABH2 and over 200 other proteins.
- APIM was functionally verified in five proteins involved in DNA maintenance, transcription, and cell cycle regulation.
- Expression of an APIM peptide enhanced cellular sensitivity to cytostatic agents, indicating a broader role than just the hABH2-PCNA interaction.
Conclusions:
- APIM is a newly discovered motif mediating PCNA binding in a wide range of proteins.
- This motif plays a significant role in DNA repair and cell cycle control, particularly during genotoxic stress.
- APIM represents a critical interaction interface for proteins involved in maintaining genomic stability.
Related Concept Videos
01:49Conserved Binding Sites
Many proteins’ biological role depends on their interactions with their ligands, small molecules that bind to specific locations on the protein known as ligand-binding sites. Ligand-binding sites are often conserved among homologous proteins as these sites are critical for protein function.
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally analyses the...
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally analyses the...
01:49Conserved Binding Sites
Many proteins’ biological role depends on their interactions with their ligands, small molecules that bind to specific locations on the protein known as ligand-binding sites. Ligand-binding sites are often conserved among homologous proteins as these sites are critical for protein function.
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally analyses the...
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally analyses the...
02:02Cis-regulatory Sequences
Cis-regulatory sequences are short fragments of non-coding DNA that are present on the same chromosomes as the genes that they regulate. These fragments serve as binding sites for transcriptional regulators, proteins that are responsible for controlling gene transcription and differential gene expression across cell types in eukaryotes. Cis-regulatory sequences can be close to the gene of interest or thousands of bases away in the DNA sequence; however, those sequences that are further away are...
02:02Cis-regulatory Sequences
Cis-regulatory sequences are short fragments of non-coding DNA that are present on the same chromosomes as the genes that they regulate. These fragments serve as binding sites for transcriptional regulators, proteins that are responsible for controlling gene transcription and differential gene expression across cell types in eukaryotes. Cis-regulatory sequences can be close to the gene of interest or thousands of bases away in the DNA sequence; however, those sequences that are further away are...
02:04Covalently 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.
These groups modify specific amino acids in a protein.
02:04Covalently 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.
These groups modify specific amino acids in a protein.