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Different oligomeric forms of protein phosphatase 2A activate and inhibit simian virus 40 DNA replication

A Cegielska1, S Shaffer, R Derua

  • 1Program in Human Molecular Biology and Genetics, University of Utah, Salt Lake City 84112.

Molecular and Cellular Biology
|July 1, 1994
PubMed

Insights

Different forms of protein phosphatase 2A (PP2A) holoenzymes differentially regulate simian virus 40 (SV40) DNA replication. Only specific PP2A forms activate T-antigen function, while others inhibit it, highlighting the role of regulatory B subunits.

Area of Science:

  • Molecular Biology
  • Virology
  • Biochemistry

Background:

  • Simian virus 40 (SV40) large T-antigen phosphorylation controls viral DNA replication initiation.
  • Protein phosphatase 2A (PP2A) catalytic subunit (PP2Ac) removes inhibitory phosphoryl groups from T-antigen serines 120 and 123.
  • PP2A functions as holoenzymes composed of catalytic (C), structural (A), and regulatory (B) subunits.

Purpose of the Study:

  • To investigate whether different PP2A holoenzyme compositions can modulate T-antigen function in SV40 DNA replication.
  • To determine the specific roles of PP2A subunit composition in regulating T-antigen-dependent origin unwinding.

Main Methods:

  • Assessed the ability of PP2A AC (dimeric) and ABC (heterotrimeric) forms to stimulate T-antigen function in vitro.
  • Utilized SV40 DNA replication assays focusing on origin unwinding.
  • Analyzed the phosphorylation status of T-antigen at specific serine and threonine residues.

Main Results:

  • Free PP2Ac and PP2A holoenzyme with a 72-kDa B subunit (PP2A-T72) stimulated T-antigen function.
  • PP2A holoenzyme with a 55-kDa B subunit (PP2A-T55) and dimeric PP2A (PP2A-D) inhibited T-antigen function.
  • PP2A-T72 dephosphorylated serines 120 and 123, activating T-antigen.
  • PP2A-D and PP2A-T55 dephosphorylated threonine 124, inactivating T-antigen.

Conclusions:

  • PP2A holoenzyme subunit composition critically influences T-antigen activity and SV40 DNA replication initiation.
  • Regulatory B subunits of PP2A are key determinants of T-antigen phosphorylation and function.
  • PP2A regulatory subunits may control SV40 DNA replication in infected cells.

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