• Press Release

Clipping Proteins that Package Genes May Limit Abnormal Cell Growth in Tumors

  • NEW YORK, NY
  • (November 21, 2014)

Changes to the structure of the protein histone H3.3 may play a key role in silencing genes that regulate cancer cell growth, according to a study led by researchers from the Icahn School of Medicine at Mount Sinai and published online this month in the journal Nature Communications. According to the authors, this is the first study to identify this protein as a key regulator in cellular senescence, a process in which cells stop multiplying.  

Cellular senescence has garnered significant scientific interest of late  because it may be one key to prevent the initiation of cancer. However, little is known about this process and how genes that enable cells to divide and multiply (the cell cycle) are turned off. A growing body of evidence suggests that the process of cellular senescence is driven by changes in the protein complexes called chromatin in the nuclei of cells.

Using models of senescence, researchers found that histone variant H3.3, a protein that works closely with chromatin to package and regulate genetic material within cells, and in particular its clipped form, help to silence target genes that regulate the cell cycle.  

Could the presence of this protein stop cells from dividing? Indeed using genome-wide transcriptional profiling, the researchers revealed that expression of clipped H3.3 silences genes that regulate the division and duplication of a cell.

“Cellular senescence creates a chromatin environment that represses cell multiplication, and thus cell or tumor growth, but how this happens molecularly is what we sought to discover,” said lead investigator Emily Bernstein, PhD, Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai. “What we found was that histone H3.3 and its clipped form, which lacks 21 amino acids of the histone tail and associated modifications, prevents normal cells from dividing. Clipped H3.3 may be a marker of cells that stop proliferating and has implications for cancer, in particular cancers like melanoma that have a senescence phase.”

This research was supported by a grant from the National Cancer Institute, University of Cambridge, Cancer Research UK, Hutchinson Whampoa and the Human Frontier Science Program, funds from The Ellison Medical Foundation, and a Developmental Research Pilot Project Program at Mount Sinai.

About the Tisch Cancer Institute
The Tisch Cancer Institute (TCI) is a world-class translational cancer institute established in December 2007. TCI has recruited more than 30 acclaimed physicians and researchers specializing in basic research, clinical research, and population science; built outstanding programs in solid tumor oncology; enhanced existing robust programs in hematological malignancies; and advanced the study of cancer immunology and vaccine therapy. The completion of the Leon and Norma Hess Center for Science and Medicine in 2012 is enabling the recruitment of up to 20 additional cancer researchers on two full research floors, with 48,000 square feet of space dedicated to cancer research.

To learn more about clinical trials at Mount Sinai, visit http://icahn.mssm.edu/research/clinical-trials.

About the Mount Sinai Health System

Mount Sinai Health System is one of the nation’s leading integrated academic health systems and one of the largest in the New York metropolitan area. Its comprehensive system includes seven hospitals, more than 400 outpatient practices, over 600 research and clinical laboratories, the Icahn School of Medicine at Mount Sinai, the Graduate School of Biomedical Sciences, and the Mount Sinai Phillips School of Nursing. Together, the Health System comprises approximately 48,000 employees, more than 9,000 physicians, and 8,600 nurses.

As a leading learning health system, Mount Sinai combines clinical expertise with scientific discovery to improve patient care while training the next generation of health care and biomedical leaders. The Health System provides care across every stage of life, from prenatal care through geriatrics, while advancing personalized medicine through artificial intelligence, data science, and biomedical research.

Mount Sinai is consistently recognized among the nation’s leading academic health systems for patient care, research, and education. The Mount Sinai Hospital is ranked No. 1 in New York by Newsweek and No. 5 on the magazine’s World’s Best Hospitals list. The Icahn School of Medicine at Mount Sinai ranks No. 11 among U.S. medical schools and No. 1 among freestanding medical schools for National Institutes of Health funding, reflecting the strength of its scientific enterprise and leadership in biomedical research.

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