# Regulation of Nuclear Import Through Importin Alpha Isoforms

> **NIH NIH R01** · THOMAS JEFFERSON UNIVERSITY · 2020 · $327,600

## Abstract

Project Summary
Trafficking of macromolecules between the nucleus and the cytoplasm is an essential cellular function
intimately linked to many degenerative processes that lead to disease and is emerging as a promising target
for therapeutic intervention. Over the last 30 years, dramatic progress in cell, molecular and structural biology
has been instrumental in elucidating the `design principles' of nuclear transport. Critical soluble factors
trafficking cargos through the Nuclear Pore Complex (NPC) have been identified. The organization,
architecture and assembly of the yeast NPC has been revealed. The physical principles governing passage of
macromolecules through the NPC have been deciphered. In stark contrast, far less is known about the
regulation of nuclear transport and the mechanisms of `fine-tuning' that result in spatiotemporally regulated
availability of critical signaling molecules in the cell nucleus. In this proposal, by integrating biophysical,
biochemical and functional techniques, we seek to understand how isoforms of the import adaptor importin α
regulate nuclear import of key factors of the NF-κB and Ran signaling pathways. Specifically, we propose to:
1.) Determine the mechanisms of importin α isoform selectivity for NF-κB heterodimers under physiological
conditions and in disease states; 2.) Decipher how importin α3 modulates the quaternary structure and
transport properties of the RCC1 import complex. Overall, our work will shed light on a poorly understood
chapter of nuclear transport, with the goal of exploiting nature's complex regulation to identify novel
pharmacological targets.

## Key facts

- **NIH application ID:** 9845781
- **Project number:** 5R01GM122844-03
- **Recipient organization:** THOMAS JEFFERSON UNIVERSITY
- **Principal Investigator:** Gino Cingolani
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $327,600
- **Award type:** 5
- **Project period:** 2018-03-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9845781

## Citation

> US National Institutes of Health, RePORTER application 9845781, Regulation of Nuclear Import Through Importin Alpha Isoforms (5R01GM122844-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9845781. Licensed CC0.

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