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Fox Chase Researchers Study Role of PP2A/B55α in Cellular Processes and Cancer Development

March 30, 2022

PHILADELPHIA (March 30, 2022)—In a recent study, researchers from Fox Chase Cancer Center have begun to define how PP2A/B55α recognizes its substrates, which are protein targets. The work may ultimately help the researchers identify other targets involved in cancer progression.

PP2A/B55α is an abundant protein phosphatase complex that is defined by its B55α subunit, which is deleted in a variety of epithelial cancers, including prostate, breast, and ovarian.

“Cells in the body communicate with other cells and their environments. Cells are capable of responding to many signals, which are transmitted inside the cells through signaling pathways. A major way to transmit signals in cells is the modification of proteins by adding phosphate to certain amino acids,” said Xavier Graña, PhD, lead author on the study and professor in the Cancer Signaling and Epigenetics Program at Fox Chase.

“We can view the addition of phosphate, mediated by enzymes called protein kinases, as the writing, and the removal of it by protein phosphatase enzymes as erasing. Alterations in these protein enzymes disrupt normal signaling, contributing to cancer development,” added Graña, who is also a professor at the Fels Cancer Institute for Personalized Medicine at the Temple University Lewis Katz School of Medicine.

Graña said his lab’s previous work has found that cancer cells that have lost one copy of B55α are very sensitive to the process of restoring it. This has led to the idea that pharmacological approaches aimed at increasing this activity may have therapeutic potential.

“This is promising, but not completely understood. So this new work will allow us to identify other targets of B55α that might be involved in cancer progression. While our understanding of how kinases recognize their protein targets is quite detailed, the same is not true for some major phosphatases,” said Graña.

“My lab is interested in addressing this gap of knowledge. What we have done is we’ve started to define how PP2A/B55α recognizes a target by binding to a conserved amino acid sequence, best described as short linear motif, or SLiM,” he said.

He added that his lab’s work suggests that many proteins key to the cell cycle, including tumor-suppressant proteins, may have this signature. Therefore, the work done by his lab can provide key insights into the way PP2A/B55α recruits its substrates and engages them in the enzyme active site. In addition, this work may facilitate identification and validation of new substrates, a key step toward understanding PP2A/B55α’s role in multiple cellular processes, the authors noted.

The study, “PP2A/B55α Substrate Recruitment as Defined by the Retinoblastoma-Related Protein p107,” was published in the journal eLife.

Fox Chase Cancer Center (Fox Chase), which includes the Institute for Cancer Research and the American Oncologic Hospital and is a part of Temple Health, is one of the leading comprehensive cancer centers in the United States. Founded in 1904 in Philadelphia as one of the nation’s first cancer hospitals, Fox Chase was also among the first institutions to be designated a National Cancer Institute Comprehensive Cancer Center in 1974. Fox Chase is also one of just 10 members of the Alliance of Dedicated Cancer Centers. Fox Chase researchers have won the highest awards in their fields, including two Nobel Prizes. Fox Chase physicians are also routinely recognized in national rankings, and the Center’s nursing program has received the Magnet recognition for excellence five consecutive times. Today, Fox Chase conducts a broad array of nationally competitive basic, translational, and clinical research, with special programs in cancer prevention, detection, survivorship, and community outreach. It is the policy of Fox Chase Cancer Center that there shall be no exclusion from, or participation in, and no one denied the benefits of, the delivery of quality medical care on the basis of race, ethnicity, religion, sexual orientation, gender, gender identity/expression, disability, age, ancestry, color, national origin, physical ability, level of education, or source of payment.

 

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