Fig. 7

Proposed mechanisms of phosphatase and tensin homolog-serine/threonine kinase 11 (PTEN-STK11) and PTEN-NUAK family kinase 1 (NUAK1) synthetic sickness/lethality. Shown are hypothesized effects of STK11 and NUAK1 loss of function on cell cycle progression (upper panels) and DNA damage repair (lower panels) in PTEN- cells. a Roles of selected genes in PTEN+ cells for comparison. b In PTEN- cells, AKT signaling is not inhibited by PTEN, leading to increased activation of NUAK1 (double blue arrows), and increased cell-cycle progression (double blue arrows and upward-pointing red arrow in top panel). The PTEN contribution to DNA damage repair is lost (faded gray oval and arrow in bottom panel). c In PTEN- cells without STK11, cell cycle progression is even more accelerated, due to loss of STK11-NUAK1 inhibition (faint orange activation and inhibition arcs in top panel). DNA damage repair is further suppressed relative to PTEN- cells with STK11 activity because of lack of activation of NUAK1 by STK11 (faint orange arrows in bottom panel). d In PTEN cells without NUAK1, cell cycle progression is arrested (top panel). DNA damage repair is suppressed relative to PTEN- cells with NUAK1 due to loss of NUAK activity (bottom panel)