Download Name of Student:

Name of Student:
Dominik Sommerfeld
Research Supervisor: Dr. Catherine Pallen
Title of Presentation: The role of specific Protein Phosphatase 2A (PP2A) holoenzymes in
orchestrating the cell cycle symphony
Abstract
Protein phosphatase 2A (PP2A), a highly abundant, ubiquitous and conserved Ser/Thr-specific
phosphatase, has been shown to regulate a plethora of important cellular processes, including
the cell cycle progression. PP2A is a heterotrimeric holoenzyme complex composed of a
catalytic subunit, a scaffolding subunit, and a variable, regulatory subunit. Genetic alterations
in the scaffolding subunit and genomic deletions or loss of heterozygosity (LOH) of regulatory
subunits have been identified in various cancers, including breast, ovarian and cervical
carcinomas. In particular, recurrent genomic deletions of the PPP2R2A (B55alpha) and
PPP2R3B (PR70/48) subunits have been found in specific subtypes of luminal breast and
endometrial carcinoma. Therefore, it is likely that dysregulation or dysfunction of PP2A
holoenzymes containing these specific subunits plays an important role in these cancers. Many
potential downstream targets of PP2A dysregulation have been reported, including cell cycle
regulators. Specifically, the B55alpha regulatory subunit has been implicated in the regulation
of mitotic entry and exit, while the PR70/48 subunit is believed to be involved in regulation of
DNA replication. Our aim is to investigate the functional consequences of loss of the B55alpha
and PR70/48 subunits on cell cycle control, and to elucidate underlying molecular pathways,
so as to gain insight into the roles of PP2A genetic alterations in cancer.