# Identification of F-Box Proteins in Toxoplasma

> **NIH NIH R21** · STATE UNIVERSITY OF NEW YORK AT BUFFALO · 2020 · $247,750

## Abstract

The SKP1/Cullin/F-box (SCF) class of E3 Ubiquitin Ligases is an evolutionarily
conserved family of enzymes that regulate key cellular processes including the cell
cycle, membrane trafficking, and signaling. The SCF-E3 is composed of four core
components - Rbx1, Cullin1, SKP1, and a F-box protein. F-box proteins are the
subunits that recruit substrate proteins to be poly-ubiquitinated by the SCF-E3, and they
can also be directly poly-ubiquitinated. SCF-E3 dependent polyubiquitin serves as a
signal for targeting to and degradation by the 26S-proteasome. Every eukaryote
expresses a repertoire of F-box proteins, the majority of which have different affinities
for different substrate proteins. Thus, F-box proteins are critical since they dictate which
specific proteins will be ubiquitinated by the SCF-E3. In addition, F-box proteins can
function independently of the SCF-E3. Thus, identifying and characterizing F-box
proteins is central to understanding the functions of the SCF-E3 and remodeling of the
proteome as cells engage new functions. This is important because protein degradation
is as important as gene transcription in defining a cell's proteome. Here, we will identify
essential SCF-E3 dependent F-box proteins, determine why they are essential, and
identify the proteins that are their ubiquitination substrates. These studies will reveal
how ubiquitin supports growth and virulence of a major human parasite. In addition,
these findings will be relevant to related pathogens given the conservation of the SCF-
E3 and many F-box proteins between Toxoplasma and other apicomplexan parasites.

## Key facts

- **NIH application ID:** 9974899
- **Project number:** 1R21AI149405-01A1
- **Recipient organization:** STATE UNIVERSITY OF NEW YORK AT BUFFALO
- **Principal Investigator:** Ira J Blader
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $247,750
- **Award type:** 1
- **Project period:** 2020-02-07 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9974899

## Citation

> US National Institutes of Health, RePORTER application 9974899, Identification of F-Box Proteins in Toxoplasma (1R21AI149405-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9974899. Licensed CC0.

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