High impact information on TPD3

• We have also determined that yeast cells contain a ceramide-activated protein phosphatase composed of regulatory subunits encoded by TPD3 and CDC55 and a catalytic subunit encoded by SIT4 [1].
• Inactivation of Cdc55 or Tpd3 enhances in vivo phosphorylation of Tap42 [2].
• Furthermore, Cdc55 and Tpd3 promote dephosphorylation of Tap42 [2].
• The predicted amino acid sequence of the product of TPD3 is highly homologous to the sequence of the mammalian A subunit of protein phosphatase 2A [3].
• Consistent with this in vivo phenotype, extracts of tpd3 strains fail to support in vitro transcription of tRNA genes, a defect that can be reversed by addition of either purified RNA polymerase III or TFIIIB [3].

Biological context of TPD3

• Therefore, the mitotic checkpoint activity of CDC55 (and TPD3) is independent of regulated phosphorylation of Cdc28p [4].
• Computer modeling of PP2Ac structure revealed that interfering amino acid substitutions clustered to the active site, and consistently, the PP2Ac-L199P mutant protein was catalytically impaired despite binding Tpd3p [5].
• We found the following: the level of each subunit remained constant throughout the cell cycle; there is at least 10 times more of one of the regulatory subunits (Rts1p) than the other (Cdc55p); Tpd3p, the structural subunit, is limiting for both catalytic and regulatory subunit binding [6].

Other interactions of TPD3

• The scaffolding A/Tpd3 subunit and high phosphatase activity are dispensable for Cdc55 function in the Saccharomyces cerevisiae spindle checkpoint and in cytokinesis [7].

References