In contrast to most genomic DNA in mitotic cells, the promoter regions of some genes, such as the stress-inducible hsp70i gene that codes for a heat shock protein, remain uncompacted, a phenomenon called bookmarking. Here we show that hsp70i bookmarking is mediated by a transcription factor called HSF2, which binds this promoter in mitotic cells, recruits protein phosphatase 2A, and interacts with the CAP-G subunit of the condensin enzyme to promote efficient dephosphorylation and inactivation of condensin complexes in the vicinity, thereby preventing compaction at this site. Blocking HSF2-mediated bookmarking by HSF2 RNA interference decreases hsp70i induction and survival of stressed cells in the G1 phase, which demonstrates the biological importance of gene bookmarking.

Members of the phosphoprotein phosphatase family of serine/threonine phosphatases are thought to exist in different native oligomeric complexes. Protein phosphatase 2A (PP2A) is composed of a catalytic subunit (PP2Ac) that complexes with an A subunit, which in turn also interacts with one of many B subunits that regulate substrate specificity and/or (sub)cellular localization of the enzyme. Another family member, protein phosphatase 5 (PP5), contains a tetratricopeptide repeat domain at its N terminus, which has been suggested to mediate interactions with other proteins. PP5 was not thought to interact with partners homologous to the A or B subunits that exist within PP2A. However, our results indicate that this may not be the case. A yeast two-hybrid screen revealed an interaction between PP5 and the A subunit of PP2A. This interaction was confirmed for endogenous proteins in vivo using immunoprecipitation analysis and for recombinant proteins by in vitro binding experiments. Our results also indicate that the tetratricopeptide repeat domain of PP5 is required and sufficient for this interaction. In addition, immunoprecipitated PP5 contains associated B subunits. Thus, our results suggest that PP5 can exist in a PP2A-like heterotrimeric form containing both A and B subunits.The reversible phosphorylation of proteins, catalyzed by protein kinases and phosphatases, is a major mechanism for regulating many cellular processes, including intermediary metabolism, cell cycle progression, DNA replication, transcription, and protein translation (1-3). It is estimated that one-third of all cellular proteins undergo reversible phosphorylation, which cells utilize to regulate the functional properties of key regulatory proteins involved in specific pathways (4).Based on homology of amino acid sequences and the similarity of three-dimensional structures, phosphoprotein phosphatases (PPPs) 1 are divided into three families designated PPP, PPM, and PTP (5, 6). The PPP and PPM families are comprised of phosphoserine-and phosphothreonine-specific enzymes, whereas the PTP family is comprised of phosphotyrosine-specific and/or dual specificity phosphatases. As suggested by the name, dual specificity phosphatases can dephosphorylate all three phosphoresidues (7). Protein phosphatase 2A (PP2A) together with PP1, PP2B (calcineurin), PP4, PP5, PP6, and PP7 are classified in the PPP family (4). PP2A exists as a heterotrimer composed of a catalytic subunit (PP2Ac), an A subunit (also known as PR65), and a B subunit. There are three major families of B subunits, PR55/B, PR61/BЈ, PR72/BЉ, with multiple isoforms within each family (4 -6, 8). The association of PP2Ac with different B subunits modulates the activity, substrate specificity, and/or (sub)cellular location of the holoenzymes, enabling them to control numerous cellular functions (3, 4, 9, 10).Protein phosphatase 5 (PP5), another member of the PPP family of phosphatases, differs from the other serine/threonine phosphatases in that it contains regulatory and (sub)cellular targetin...

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