Mysterious ‘nuclear speckle’ cell structures may help block cancers

A new study out of Penn Medicine shows that the tumor-suppressor protein p53 brings speckles and DNA together to boost gene expression.

A team led by scientists at the Perelman School of Medicine has illuminated the functions of mysterious structures in cells called “nuclear speckles,” showing that they can work in partnership with a key protein to enhance the activities of specific sets of genes.

Left image: microscopic nucleus of a cell. Right image: Illuminated nuclear speckles surrounding the nucleus of a cell.
This image of cells shows p53 induction of a key p53 target. On the left are cells where p53 is not active; on the right, p53 has been activated. Each small green spot shows a single mRNA of the p53 target gene. The site where the gene is being transcribed in the nucleus is the bright green spot. Nuclear speckles are shown in red. (Image: Penn Medicine News)

The discovery, published in Molecular Cell, is an advance in basic cell biology; the key protein it identifies as a working partner of speckles is best known as major tumor-suppressor protein, p53. This avenue of research may also lead to a better future understanding of cancers, and possibly better cancer treatments.

“This study shows that nuclear speckles work as major regulators of gene expression, and suggests that they have a role in some cancers,” says study senior author Shelley Berger, the Daniel S. Och University Professor in the Department of Cell and Developmental Biology.

The research goes even further to show that the p53 target genes whose activity is boosted via speckles have a set of functions that are broadly distinct from those of other p53 target genes.

In the study, Berger and colleagues, including first author Katherine Alexander, a postdoctoral researcher in the Berger Laboratory who did most of the experiments, overcame some of these challenges to reveal that speckles work with p53 to directly enhance the activity of certain genes.

“Speckle-associated p53 target genes, compared to other p53 target genes, are more likely to be involved in tumor-suppressing functions, such as stopping cell growth and triggering cell suicide,” Alexander says.

This story is by Sophie Kluthe. Read more at Penn Medicine News.