SCF (Skp, Cullin, F-box) E3 ubiquitin ligase complexes are key players in controlling mitotic cell cycle transitions. We found SCFPROM-1 functions in the transition of mitotic cycling progenitor zone cells to meiotic development. Previous work identified a regulatory network where
glp-1 Notch signaling promotes the stem cell fate by inhibiting the
gld-1 and
gld-2 translational regulatory pathways that function redundantly to promote meiotic development. However, genetic analysis indicated that activities in addition to the
gld-1 and
gld-2 pathways are also necessary for the transition. We found that
skr-2 (Skp),
cul-1 (Cullin) and
prom-1 (F-box) are required for downregulation of CYE-1 (cyclin E), WAPL-1 (cohesin chaperone), KNL-2 (kinetochore assembly) and pCDC-6 (DNA replication), that occurs at the boundary of the progenitor zone and leptotene/zygotene. We showed that PROM-1 induces polyubiquitination of CYE-1 in a cell culture based assay. Together, these results indicate that PROM-1 is acting as a specificity subunit for
skr-2 and
cul-1 (SCFPROM-1) in the degradation of CYE-1 at meiotic entry, and by extension, the degradation of WAPL-1 and KNL-2. We also found that SCFPROM-1 is necessary for homologous chromosome pairing, acting upstream or in parallel to CHK-2, a key regulator of the initiation of meiotic chromosome pairing. While SCFPROM-1 mutant hermaphrodites display ectopic mitotic proteins (CYE-1, etc) proximal to the progenitor zone, these cells are not mitotically cycling and express meiotic proteins HIM-3 (axis protein) and COH-3/-4 (meiotic cohesin). By contrast in SCFPROM-1 mutant males, cells proximal to the progenitor zone that express mitotic proteins are mitotically cycling, although they express meiotic proteins HIM-3 and COH-3/-4. These results indicate that SCFPROM-1 functions to down regulate mitotic activity at meiotic entry, as well as promote meiotic chromosome pairing. As these two activities are important for initiation of meiotic development, then SCFPROM-1 may act in parallel to the
gld-1 and
gld-2 pathways to promote the switch to meiotic development. In support of this hypothesis we find that (a) SCFPROM-1 double mutants with
gld-1 pathway genes show ectopic proliferation; (b) SCFPROM-1 double mutants with
gld-2 pathway genes show ectopic proliferation; (c) the ectopic proliferation found in SCFPROM-1 double mutants with
gld-1 or
gld-2 pathway genes is epistatic to the premature meiotic entry phenotype of
glp-1 null; and (d) SCFPROM-1 mutants enhance the meiotic entry defect (overproliferation) observed in
gld-1 gld-2 pathway double mutants. Thus C. elegans employs three posttranscriptional pathways, SCFPROM-1 mediated protein degradation, GLD-1 mediated translational repression and GLD-2 mediated translational activation to promote the initiation of meiotic development.