# Post-translational Regulation of Inducible cAMP Early Repressor and its Implications in Cancer

> **NIH NIH SC1** · MONTCLAIR STATE UNIVERSITY · 2021 · $321,219

## Abstract

Project Summary/Abstract
 Even though Inducible cAMP Early Repressor (ICER) has the functional characteristics of a tumor
suppressor, there is no genetic evidence to demonstrate that ICER is a bona fide tumor suppressor gene
product. Thus, altered post-translational events might be the cause of the observed abnormalities of ICER
protein expression in cancer cells. On this basis it is hypothesized that in cancer cells, ICER is
deregulated by ubiquitination resulting in constitutive proteasomal degradation and/or abnormal
subcellular localization. Finding alternatives to rescue endogenous ICER nuclear expression in malignant
cells could lead to the development of novel cancer treatment modalities. Through this project, we will study
the mechanisms and physiological consequences of ICER ubiquitination and subcellular localization. We will
use melanoma as a paradigm for the study. This study will focus on two specific aims.
Aim 1. Determine the functional and physiological consequences of ICER ubiquitination by
characterizing the specific ubiquitination sites on ICER and ubiquitin E3 ligases using biochemistry,
chromatin binding, and siRNA techniques.
Aim 2. Examine the effect on tumorgenesis upon expression of “ubiquitinatable”-deficient ICER using
mouse xenograft models and an established zebrafish model for melanoma.
 The overarching goal of this project is to determine the functional consequences of ICER post-
translational modifications in cancer. The experiments described in this proposal will provide the basis for more
extensive analyses of multi-component complexes associated with the regulation of ICER in cancer cells.
Subsequent research will: 1) Use the zebrafish melanoma model to further characterize the molecular
mechanisms of ICER ubiquitination during melanoma genesis; 2) Establish collaborative efforts to develop
small-molecule compounds and small ICER-related peptides as specifics Ub-ligases inhibitors to test specific
approaches to restore endogenous ICER nuclear expression in cancer cells; and 3) Study the effect of these
Ub-ligase inhibitors in animal models for cancer.

## Key facts

- **NIH application ID:** 10147097
- **Project number:** 5SC1GM125583-04
- **Recipient organization:** MONTCLAIR STATE UNIVERSITY
- **Principal Investigator:** CARLOS A MOLINA
- **Activity code:** SC1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $321,219
- **Award type:** 5
- **Project period:** 2018-05-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10147097

## Citation

> US National Institutes of Health, RePORTER application 10147097, Post-translational Regulation of Inducible cAMP Early Repressor and its Implications in Cancer (5SC1GM125583-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10147097. Licensed CC0.

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