# Regulation of cell cycle transition by a cyclin-dependent kinase in trypanosomes

> **NIH NIH R01** · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · 2020 · $385,000

## Abstract

Cyclin-dependent kinases (CDKs) are the fundamental regulators of the cell cycle in eukaryotes, which
are activated by binding to cyclins whose abundance changes during the cell cycle. A single cyclin and multiple
CDKs function in yeast cell cycle control, whereas multiple cyclins and multiple CDKs control the cell cycle
progression in animals. Trypanosomes appear to employ a cell cycle control system that is strikingly different
from that in fungi and animals. A PHO80-like cyclin, CYC2, and a CDK-related kinase, CRK1, control the G1/S
transition, whereas a B-type cyclin, CYC6, and another CDK-related kinase, CRK3, govern the G2/M transition.
However, how CRK1 exert their roles in cell cycle progression remains elusive, mainly because its downstream
targets are not known. The current proposal aims to understand the mechanisms underlying the G1/S cell
cycle transition and the molecular basis for the distinct cell cycle regulation between different life cycle forms of
T. brucei. In aim 1 of this proposal, we plan to apply chemical genetic approach to identify CRK1 substrates
from the procyclic and bloodstream forms and to comparatively analyze the CRK1-regulated cellular pathways
between the two forms. Aim 2 is to understand the mechanisms underlying the cell cycle-dependent protein
translation initiation, with a focus on the regulation of two translation initiation factors by CRK1. Aim 3 is to
dissect the role of CRK1 in DNA replication initiation by investigating CRK1-mediated regulation of the DNA
replication factors in the Cdc45-Mcm2-7-GINS complex. Through molecular, cell biological, chemical genetic,
and biochemical approaches, our overall goal in this proposal is to understand the mechanistic roles of CRK1
in the G1/S control through regulating the DNA replicative helicase and in G1-specific protein translation
initiation through regulating translation initiation factors. The outcomes from these studies not only will
significantly advance our understanding of the mechanisms of cell cycle transitions in trypanosomes, but also
could validate CRK1 and its trypanosome-specific downstream pathways as drug targets for anti-trypanosome
chemotherapy.

## Key facts

- **NIH application ID:** 9896765
- **Project number:** 5R01AI118736-05
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
- **Principal Investigator:** Ziyin Li
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $385,000
- **Award type:** 5
- **Project period:** 2016-05-13 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9896765

## Citation

> US National Institutes of Health, RePORTER application 9896765, Regulation of cell cycle transition by a cyclin-dependent kinase in trypanosomes (5R01AI118736-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9896765. Licensed CC0.

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