# Impacting Cell Growth through altered circadian proteolysis

> **NIH NIH R01** · SCRIPPS RESEARCH INSTITUTE, THE · 2021 · $2,946

## Abstract

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 awell-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:** 10367294
- **Project number:** 3R01CA211187-04S1
- **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:** $2,946
- **Award type:** 3
- **Project period:** 2017-08-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10367294

## Citation

> US National Institutes of Health, RePORTER application 10367294, Impacting Cell Growth through altered circadian proteolysis (3R01CA211187-04S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10367294. Licensed CC0.

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