Related Experiment Video

Updated: Aug 17, 2026

In vivo Application of the REMOTE-control System for the Manipulation of Endogenous Gene Expression
08:54

In vivo Application of the REMOTE-control System for the Manipulation of Endogenous Gene Expression

Published on: March 29, 2019

Molecular mechanism of Reaper-Grim-Hid-mediated suppression of DIAP1-dependent Dronc ubiquitination

Jijie Chai1, Nieng Yan, Jun R Huh

  • 1Department of Molecular Biology, Princeton University, Lewis Thomas Laboratory, Washington Road, Princeton, New Jersey 08544, USA.

Nature Structural Biology
|October 1, 2003
PubMed

Insights

The inhibitor of apoptosis protein DIAP1 binds Dronc to prevent cell death. Pro-apoptotic RHG proteins disrupt this interaction, promoting apoptosis by blocking DIAP1 ubiquitination of Dronc.

Area of Science:

  • Cellular Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Inhibitor of apoptosis proteins (IAPs) like DIAP1 regulate cell death pathways.
  • DIAP1 inhibits apoptosis by ubiquitinating and targeting caspases, such as Dronc, for degradation.
  • Pro-apoptotic proteins Reaper, Hid, and Grim (RHG) counteract IAP function to promote programmed cell death.

Purpose of the Study:

  • To elucidate the structural basis of Dronc recognition by DIAP1.
  • To uncover the molecular mechanism by which RHG proteins antagonize DIAP1.
  • To explain how RHG proteins remove DIAP1-mediated inhibition of Dronc.

Main Methods:

  • Biochemical analyses
  • Structural analyses (e.g., X-ray crystallography)
  • Protein-protein interaction studies

Main Results:

  • DIAP1's second BIR domain (BIR2) binds a specific 12-residue sequence on Dronc.
  • This BIR2-Dronc interaction is crucial for Dronc ubiquitination by DIAP1.
  • RHG proteins bind to the same BIR2 surface, competitively inhibiting Dronc ubiquitination.

Conclusions:

  • DIAP1 recognizes Dronc via its BIR2 domain, leading to Dronc ubiquitination and inhibition of apoptosis.
  • RHG proteins disrupt DIAP1-Dronc binding by competing for the BIR2 binding site.
  • This competitive binding mechanism explains how RHG proteins reverse DIAP1-mediated suppression of Dronc, thereby promoting apoptosis.

More Related Videos

Lentiviral Vector Platform for the Efficient Delivery of Epigenome-editing Tools into Human Induced Pluripotent Stem Cell-derived Disease Models13:47

Lentiviral Vector Platform for the Efficient Delivery of Epigenome-editing Tools into Human Induced Pluripotent Stem Cell-derived Disease Models

Published on: March 29, 2019

In Vitro Selection of Engineered Transcriptional Repressors for Targeted Epigenetic Silencing10:44

In Vitro Selection of Engineered Transcriptional Repressors for Targeted Epigenetic Silencing

Published on: May 5, 2023

Related Concept Videos

Co-activators and Co-repressors02:04

Co-activators and Co-repressors

Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
Eukaryotic Transcription Inhibitors01:52

Eukaryotic Transcription Inhibitors

Certain biochemical processes, such as embryonic development and cell growth regulation, depend on the repression of specific genes. DNA binding proteins known as eukaryotic transcription inhibitors regulate the repression of gene expression in eukaryotes. The presence of these inhibitors at the required location and time in the cell is triggered by the presence of hormones and additional signals from other cells.
Eukaryotic transcription inhibitors usually contain two distinct domains, a DNA...
Exon Recombination02:32

Exon Recombination

The evolution of new genes is critical for speciation. Exon recombination, also known as exon shuffling or domain shuffling, is an important means of new gene formation. It is observed across vertebrates, invertebrates, and in some plants such as potatoes and sunflowers. During exon recombination, exons from the same or different genes recombine and produce new exon-intron combinations, which might evolve into new genes. 
Exon shuffling follows “splice frame rules.” Each exon has three reading...
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...
The Unfolded Protein Response01:37

The Unfolded Protein Response

The ER is the hub of protein synthesis in a cell. It has robust systems to quality control protein folding and also for degradation of terminally misfolded proteins. Under normal conditions, a small proportion of misfolded proteins that cannot be salvaged need to be transported to the cytoplasm by the ER-associated degradation or ERAD pathways. However, if the ERAD cannot handle the misfolded proteins, the cell activates the unfolded protein response or UPR to adjust the protein folding...
Regulation of the Unfolded Protein Response01:31

Regulation of the Unfolded Protein Response

Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...