# Decoding the non-canonical polyubiquitin chains using chemical approaches

> **NIH NIH R01** · UNIVERSITY OF DELAWARE · 2021 · $303,171

## Abstract

Decoding the noncanonical polyubiquitin chains using chemical approaches
 The ubiquitin system is crucial for the regulation of a wide range of cellular and organismal functions
essential for the human health. Although our knowledge of the ubiquitin system initially stems from the
investigation into proteasome-mediated protein degradation, it has become clear that ubiquitination is also
indispensible for many non-proteolytic functions. Many noncanonical ubiquitin chains are associated with
cellular functions other than protein degradation. The K63-linked polyubiquitin chain in DNA damage tolerance
has been found to be signal for the eukaryotic error-free lesion bypass. However, little is known as to how this
signal regulates the DNA damage tolerance pathways. The downstream proteins that decode the K63-
polyubiquitin signals on PCNA still need to be identified. In order to decipher the diverse cellular roles of
polyubiquitination, chemical approaches of generating polyubiquitinated proteins and noncanonical ubiquitin
chains with defined structure and length are needed. This will lead to the discovery of the downstream reader
proteins in DNA damage tolerance and other important cellular processes. It will also enable in-depth
biochemical and biophysical characterizations of the recognition of noncanonical polyubiquitin chains by the
reader proteins. This will broaden our understanding of the many biological processes regulated by
ubiquitination and furnish new pathways and targets amenable for therapeutic intervention.

## Key facts

- **NIH application ID:** 10115076
- **Project number:** 5R01GM129468-03
- **Recipient organization:** UNIVERSITY OF DELAWARE
- **Principal Investigator:** Zhihao Zhuang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $303,171
- **Award type:** 5
- **Project period:** 2019-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10115076

## Citation

> US National Institutes of Health, RePORTER application 10115076, Decoding the non-canonical polyubiquitin chains using chemical approaches (5R01GM129468-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10115076. Licensed CC0.

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