Enzymatic Cascade & Protein Fate

Ubiquitin Proteasome System (UPS)

The ubiquitin proteasome system (UPS) is a highly conserved system of the cell that performs many essential functions composed as a cascade of many enzymes that tag the C-terminal of ubiquitin to target proteins.

Essential Cellular Quality Control

The ubiquitin proteasome system (UPS) is highly conserved system of the cell that performs many essential functions composed as a cascade of many enzymes that tag the C-terminal of ubiquitin (a highly conserved protein) to target proteins. Frequently, these chains of poly-ubiquitins are built on target proteins.

Pathway Architecture

The Ubiquitin-Proteasome Cascade & Degradation Routes

Sequential transfer of ubiquitin via E1, E2, and E3 enzymes directing cellular fate toward proteasomal or lysosomal clearance.

1. Activation (E1)

ATP-dependent ubiquitin charging

2. Conjugation (E2)

Intermediate thioester transfer

Target substrate specificity

Ubiquitin chain editing & recycling

Poly-Ubiquitin Specificity

Differential Chain Linkages & Cellular Fates

Distinct topologies redirecting proteins toward lysosomal degradation or nuclear transcription.

Lysine 63 Topology

Chains of lysine 63 poly-ubiquitins on damaged or misfolded proteins lead to degradation of proteins or organelles such as mitochondria by lysosomes (mitophagy).

Outcome: Lysosomal clearance & organelle recycling

Lysine 48 Topology

Lysine 48 linked poly-ubiquitin chains promote target protein degradation by proteasome. Such as degradation of repressor protein in cell nucleus that unleashes PGC1 α a transcription factor that transcribes all the nuclear mitochondrial genes and leads to mitobiogenesis.

Outcome: Proteasomal degradation & PGC1 α gene activation

Myto Health Toolbox of Affinity Matrices

Myto Health has established a toolbox of affinity matrices to identify all types of ubiquitin signatures that are hallmarks of disease in humans. This toolbox is employed to establish and discover neurodegenerative biomarkers from blood.

The toolbox is essential for developing assays for ubiquitin ligases and de-ubiquitylases (DUBs). The ligase toolbox is exploited to discover small molecule drugs that promote mitophagy and mitobiogenesis as well as discover natural products and nutraceuticals that improve mitochondrial health and aging.

Employed to identify and capture trace poly-ubiquitin disease signatures directly from peripheral circulation.

Essential framework for quantifying activity profiles across ubiquitin ligases and de-ubiquitylating enzymes.

Exploited to screen and validate therapeutic modulators that trigger organelle renewal and healthy aging.

Access the Ubiquitin Toolbox & Assays

Inquire with our scientific team in Malvern, PA about affinity matrices, MTA agreements, or assay licensing.