Survivin and Caspases Coordinate Proteolytic Cleavage of the SAGA Chromatin Modifying Complex

Authors

Elinor Harrison, Wayne State University School of MedicineFollow
Alejandro Damian, Wayne State University School of MedicineFollow
CJ Talton, Wayne State University School of MedicineFollow

Research Mentor Name

Dr. Ryan Mohan

Research Mentor Email Address

RDM@wayne.edu

Institution / Department

Wayne State University School of Medicine/Department of Pharmacology

Document Type

Research Abstract

Research Type

basicbio

Graduate Level Research

no

Abstract

Title: Survivin and Caspases Coordinate Proteolytic Cleavage of the SAGA Chromatin Modifying Complex

Elinor Harrison¹, Alejandro Damian¹, CJ Talton¹, Jelly H Soffers¹, Abudu I Bello¹, Kara M Costanzo¹, Joe Bean¹, Ryan D Mohan¹

¹Wayne State University School of Medicine

Background: The Spt Ada Gcn5 Acetyltransferase (SAGA) chromatin modifying complex is a critical regulator of gene expression. Mutation or stoichiometric imbalance of SAGA subunits leads to a spectrum of diseases in model organisms and in humans, including neurodegeneration. SAGA contributes to gene activation through coordinated function of intrinsic histone-acetyltransferase and deubiquitinase activities which are housed within distinct, functionally independent, modules. Although much is understood about how acetylation effects SAGA function, mechanisms regulating SAGA deubiquitinase module remain unknown.

Methods: To identify pathways working to prevent proteolytic cleavage, we performed a biochemical interaction screen to locate novel interactors of SAGA.

Results: The screen identified the Survivin protein which possesses a Baculoviral IAP Repeat (BIR) domain characteristic of Inhibitor of Apoptosis Proteins (IAP). IAPs function as decoys by competitively binding to caspases via their BIR domains, locally preventing caspase-mediated cleavage. SAGA bears two caspase cleavage sites on SAGA subunit Atxn7. Preliminary data show loss of Survivin results in proteolytic cleavage of Drosophila Atxn7 like that seen when mammalian Atxn7 is proteolytically cleaved by Caspase-7.

Conclusion: These findings identify Survivin as a protein that limits proteolytic cleavage of SAGA, suggesting a potential pathway that is protective of nervous system health.

Disciplines

Cell Biology | Medicine and Health Sciences | Molecular and Cellular Neuroscience | Nervous System Diseases

Recommended Citation

Harrison, Elinor; Damian, Alejandro; and Talton, CJ, "Survivin and Caspases Coordinate Proteolytic Cleavage of the SAGA Chromatin Modifying Complex" (2026). Medical Student Research Symposium. 483.
https://digitalcommons.wayne.edu/som_srs/483