# Roles and Regulation of the bZip Transcription Factor CEBP-1 in Stress Response Pathways

> **NIH NIH F31** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2020 · $38,395

## Abstract

Project Summary
Proper cellular response to stress is vital for organismal survival. Most cellular stress responses involve the
action of transcription factors that regulate expression of stress response genes. Determining how transcription
factors can initiate differential responses to a variety of stressful inputs is critical for understanding multiple
human diseases. The overall goal of this project is to uncover the mechanisms by which a single
transcription factor can integrate multiple inputs and direct proper transcriptional responses. CCAAT
enhancer binding proteins (C/EBP) family proteins are involved in many forms of stress responses. C/EBPs
contain a basic-leucine-zipper DNA binding domain, and transactivating and regulatory domains, which modulate
transcriptional activity via specific protein-protein interactions or post-translational modifications. Although
C/EBP proteins have been extensively studied, the mechanism of their action under external stimuli is still poorly
understood. Studies using Caenorhabditis elegans offer great advantages to investigate multi-level cellular and
organismal responses to stress signals. This proposal focuses on examining the molecular function of the
conserved C/EBP homologue, CEBP-1, in mediating both development and neuronal stress responses. In
neurons, CEBP-1 plays critical roles in response to axon injury and cytoskeleton disruption, acting downstream
of the DLK-1 MAP kinase cascade. In animal development CEBP-1 is negatively controlled by the Tribbles family
protein, NIPI-3, and in turn activates a different MAP kinase cascade. Using powerful forward genetic screening,
I have identified a distinct functional domain in the N-terminus of CEBP-1 that is crucial for its activity. Here, I
propose to test the hypothesis that this domain, in conjunction with differential protein-protein interaction, endows
transactivating regulation to initiate transcriptional responses to different stressful inputs. The goals of this study
will be accomplished through the following specific aims: Aim 1: To identify CEBP-1 binding proteins using IP-
mass spectrometry and to demonstrate that the N-terminal region contains transactivating activity. Aim 2: To
determine the mechanism of transcriptional regulation of CEBP-1 by NIPI-3; and Aim 3: to Identify new genetic
players in NIPi-3/Tribbles and CEBP-1 pathway. The completion of this proposal will provide a deeper
understanding of the general process of stress response to various external stimuli. Understanding the
mechanism of this control could allow for development of targeted treatments for diseases affecting cellular
stress response and repair.

## Key facts

- **NIH application ID:** 9897413
- **Project number:** 5F31GM131677-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Rose Malinow
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $38,395
- **Award type:** 5
- **Project period:** 2019-04-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9897413

## Citation

> US National Institutes of Health, RePORTER application 9897413, Roles and Regulation of the bZip Transcription Factor CEBP-1 in Stress Response Pathways (5F31GM131677-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9897413. Licensed CC0.

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