Inactivation of tumour suppressors is an essential step during tumorigenesis. Permanent genetic alterations inactivate p53 and other class I tumour suppressor genes; reversible mechanisms, which could provide targets for cancer therapy, inactivate class II tumour suppressors. Now, Christine Sers and colleagues reveal how the type II tumour suppressor HRSL3 (also called H-REV107-1) might regulate the growth and survival of ovarian cancer cells (see p. 1393). HRSL3 is expressed in most normal tissues but downregulated in many human tumours. The authors show that it sequesters a regulatory subunit of protein phosphatase 2A (PP2A) away from the enzyme's catalytic subunit – HRSL3 interacts through its N-terminal proline-rich region with the α-isoform of regulatory subunit A of PP2A. Overexpression of HRSL3 (but not of a mutant lacking the interaction domain) reduces PP2A activity in ovarian cancer cells and induces their apoptosis. Furthermore, the HRSL3-PP2A interaction inhibits the dephosphorylation of the atypical Ca2+-dependent protein kinase PKCζ by PP2A. The authors suggest, therefore, that HRSL3 regulates a signalling pathway that drives tumorigenesis in the ovary.