# Impacting Cell Growth through altered circadian proteolysis

> **NIH NIH R01** · SCRIPPS RESEARCH INSTITUTE, THE · 2021 · $442,631

## Abstract

7. Project Summary/Abstract
Circadian clocks have recently become recognized as modulators of a wide array of
physiological processes, including glucose homeostasis, blood pressure modulation, and
cancer. In addition, it is well established through epidemiological studies that circadian
disruption increases the incidence of several types of cancer. However, the molecular basis for
these phenomena is not well understood. The underlying hypothesis of this proposal is that the
circadian clock component protein Cry2 modulates cancer risk by promoting the destruction of a
well-known cancer causing protein, the proto-oncogene c-Myc, and that environmental circadian
disruption due to shift work or chronic jet lag enhances cancer risk by altering Cry2 expression
leading to increased c-Myc activity. Advancing our functional understanding of these
interactions may highlight new therapeutic and regulatory strategies for preventing and/or
treating disease. Our previous studies identified the circadian clock component cryptochromes
(Cry1 and Cry2) as nutrient and DNA damage responsive transcriptional regulators by virtue of
their susceptibility to phosphorylation by AMP-activated protein kinase (AMPK) and DNA
damage-induced deubiquitination by Herpes virus associated ubiquitin specific protease
(Hausp, a.k.a. Usp7). Most recently, we made the unexpected discovery (described in
preliminary data here) that Cry2 is a required physical component of a complex that regulates
the stability of c-Myc by targeting it for destruction by the proteasome. In the course of our
studies, we have generated unique tools and expertise that enable us to use biochemical,
genetic, molecular and physiological approaches to uncover the roles of circadian clocks and of
the circadian protein Cry2 in cell growth and tumor development, specifically aimed at asking: 1)
Does human CRY2 protect cells from transformation by promoting degradation of MYC family
proteins? 2) What is the relative importance of repression and proteolysis in the biological
functions of Cry2? and 3) Is disruption of Cry2-dependent Myc turnover involved in increased
tumorigenesis caused by chronic jet lag or shift work?

## Key facts

- **NIH application ID:** 10226276
- **Project number:** 5R01CA211187-05
- **Recipient organization:** SCRIPPS RESEARCH INSTITUTE, THE
- **Principal Investigator:** Katja A Lamia
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $442,631
- **Award type:** 5
- **Project period:** 2017-08-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10226276

## Citation

> US National Institutes of Health, RePORTER application 10226276, Impacting Cell Growth through altered circadian proteolysis (5R01CA211187-05). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10226276. Licensed CC0.

---

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