The power of MEN in cytokinesis

Abstract

In budding yeast, the mitotic exit network (MEN) is a signaling pathway best known for its role in driving cells out of mitosis through activation of the conserved phosphatase Cdc14. However, work over the past few years show that MEN components and Cdc14 also have a direct role in promoting cytokinesis by acting upon components of the contractile actomyosin ring and cell separation machineries. In this review, we discuss the current view on the role of MEN kinases and Cdc14 in cytokinesis and comment on the cytokinesis-related function of MEN and Cdc14 orthologs in higher eukaryotes.

Hippo signalling in the G2/M cell cycle phase: Lessons learned from the yeast MEN and SIN pathways

“…Using a similar mechanism as reported for the MEN, the Mob1p/Sid2p complex directly phosphorylates Clp1p, thereby affecting the subcellular localisation of Clp1p [49]. Significantly, Clp1p might also regulate similar cytokinetic factors as reported for budding yeast Cdc14p [33,50]. In particular, the regulation of budding yeast Hof1p appears to be conserved between SIN and MEN.…”

“…By changing the phosphorylation status of the formins Bnr1 and Bni1, Cdc14p can affect the repolarisation of the cytoskeleton at the end of mitosis [42]. Cdc14p may also directly regulate Boi1, Boi2, Chs1, Shs1 and other mitotic factors to facilitate cytokinesis [33], however, the direct regulation of these proteins by Cdc14p is yet to be established. Intriguingly, Cdc14p is further required for the functionality of the LATS/ NDR kinase Cbk1p (the second LATS/NDR kinase in budding yeast) [43].…”

“…The machinery regulating the controlled exit of mitosis is highly conserved in other yeast species [33]. In particular in Schizosaccharomyces pombe, mitotic exit signalling has been extensively studied in addition to budding yeast [10,11].…”

“…On one hand, Dbf2p and Mob1p have been found at the actin-myosin ring (AMR) structure that is essential for abscission [35][36][37][38], and Cdc15p, Dbf2p and Mob1p are required for AMR contraction [39,40]. Moreover, current evidence suggests that the MEN components Dbf2p and Mob1p can regulate the cytokinetic components Chs2p, Hof1p, and Inn1p (summarised in [33,41]). However, Hof1p (one of at least three F-BAR domain proteins in S. cerevisiae) is so far the only established target of Mob1p/Dbf2p in cytokinesis [41].…”

“…In budding yeast, these efforts revealed a so-called mitotic exit network (MEN) kinase cascade [10,11,32,33]. MEN signalling triggers the transition from the mitotic anaphase through to the G1-phase of the cell cycle by inactivating mitotic CDK1, one key hallmark of the end of mitosis [5].…”