# Notch Mediated Intercellular Communication and Cell cycle Regulation

> **NIH NIH R01** · TULANE UNIVERSITY OF LOUISIANA · 2020 · $303,833

## Abstract

PROJECT SUMMARY
Coordinated regulation of cell proliferation and differentiation by signaling pathways is fundamental to
the development of multicellular organisms. Failure in such regulations frequently lead to
tumorigenesis or growth defects during development. The Notch signaling pathway mediated
intercellular communication is critical for a wide range of biological processes during normal
development and pathogenesis of numerous human diseases, including multiple types of cancer.
However, its relationship with cell cycle regulation and growth control is complex since Notch can play
either a tumor suppressor or an oncogenic role. Furthermore, little is known on whether and how the
cell cycle machinery feeds back to influence Notch signaling. The proposed studies are based on two
surprising preliminary findings on Notch regulation in the Drosophila oogenesis model system, where
Notch plays a central role in controlling the switch of the cell cycle programs from mitosis to
endoreplication cycles in epithelial follicle cells. We find that the Chromatin Assembly Factor 1 (CAF-1)
acts as both a repressor and an activator to regulate Notch target gene expression in follicle cells. We
also find that the cell cycle machinery regulates the stability of the active form of Notch, the cytoplasmic
domain NICD. On the basis of these new findings, two specific aims are proposed to determine (1) the
molecular mechanisms underlying CAF-1 regulation of Notch signaling and (2) the potential feedback
mechanisms of the cell cycle machinery on Notch stability and activity. Both aims address important
aspects of Notch regulation in relation to cell proliferation control, but can be executed separately. The
outcomes of the proposed project will lead to improved understanding of how Notch signaling and cell
cycle machinery interact during animal development and tissue homeostasis. The new insights into the
regulation of Notch signaling in the Drosophila model system will have a positive impact on biomedical
research due to the strong correlation of the Notch pathway with tumorigenesis and cancer
development. The findings from these studies will provide new conceptual understandings of how
signaling pathways exert their roles to ensure correct decisions in cellular and tissue growth,
understandings which can be used to design novel therapies for diseases related to aberrant Notch
signaling.

## Key facts

- **NIH application ID:** 9918422
- **Project number:** 5R01GM072562-14
- **Recipient organization:** TULANE UNIVERSITY OF LOUISIANA
- **Principal Investigator:** Wu-Min Deng
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $303,833
- **Award type:** 5
- **Project period:** 2006-09-01 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9918422

## Citation

> US National Institutes of Health, RePORTER application 9918422, Notch Mediated Intercellular Communication and Cell cycle Regulation (5R01GM072562-14). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/9918422. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*