# Molecular mechanisms of CIB1 signaling

> **NIH NIH R01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2020 · $308,582

## Abstract

ABSTRACT
CIB1 is an intracellular protein that regulates cell growth, survival and proliferation, most
notably under pathologic conditions. It functions by binding directly to effector kinases,
integrins and other targets and modulates their activity, thereby serving as a signaling
node for key regulatory pathways. Inhibition of CIB1 binding to select partners has
excellent therapeutic potential in multiple diseases such as cancer, retinopathies and
cardiac hypertrophy. It is therefore critical to understand CIB1 signaling in different cell
types. In many breast cancer cell lines but not in normal cells tested to date, CIB1 is
required for survival and proliferation via the PI3K/AKT and MEK/ERK pathways. In
endothelial cells, CIB1 supports efficient angiogenesis in response to injury via the
MEK/ERK pathway. However, how and why CIB1 selectively regulates these pathways
under stressed or transformed conditions is poorly understood. We found that CIB1
interacts directly with PAK1 and PDK1, which can feed into these pathways. Moreover,
while some data suggest that CIB1 regulates integrin signaling, which can activate the
PI3K/AKT and MEK/ERK pathways, it is completely unknown whether or how CIB1
connects integrin signaling to these pathways. Our overall hypothesis is that under
select stress or oncogenic conditions in a variety of cell types, CIB1 binds to specific
partners to regulate the PI3K/AKT, MEK/ERK and potentially other pathways, to
promote cell viability, growth and proliferation. To address this hypothesis, we will use a
combination of targeted and unbiased approaches to determine how the CIB1
interaction with PAK1, PDK1 and the αV integrin support the PI3K/AKT and MEK/ERK
pathways. We will complement targeted approaches with unbiased phosphoproteomics
and interactomics to delineate on a global scale, how CIB1 signaling affects not only
MEK/ERK and PI3K/AKT but other phospho-signaling pathways that may help explain
CIB1 biology.

## Key facts

- **NIH application ID:** 9994354
- **Project number:** 5R01GM133107-02
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** XIAN CHEN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $308,582
- **Award type:** 5
- **Project period:** 2019-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9994354

## Citation

> US National Institutes of Health, RePORTER application 9994354, Molecular mechanisms of CIB1 signaling (5R01GM133107-02). Retrieved via AI Analytics 2026-06-02 from https://api.ai-analytics.org/grant/nih/9994354. Licensed CC0.

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