The Retinoblastoma gene product (pRb) has been implicated in the regulation of multiple cellular and developmental processes, including a well-defined role in the control of cell cycle progression. The Caenorhabditis elegans Rb protein homolog, LIN-35, is also a key regulator of cell cycle entry (Boxem snd van den Heuvel, 2001) and, as shown by studies of Synthetic Multivulval genes, plays an important role in the determination of vulval cell fates (Lu and Horvitz, 1998). Using a genetic screen to identify mutations causing synthetic phenotypes with
lin-35/Rb in C. elegans, we previously reported the identification of mutations in
fzr-1, a regulatory subunit of the APC proteasome (Fay et al., 2002).
lin-35;
fzr-1 double mutants display a hyperproliferation phenotype affecting virtually all cell types examined. We now describe our analysis of another mutation identified by our screen,
ubc-18/slr-5. Animals harboring single mutations in
ubc-18 (
ku354) are viable and display no obvious developmental defects. An analysis of
lin-35;
ubc-18 double mutants however reveals redundant functions for these genes in the control of pharyngeal morphogenesis.
ubc-18 encodes an E2 ubiquitin-conjugating enzyme closely related to human UbcH7. Based on genetic and phenotypic analyses, this role for
lin-35 in pharyngeal morphogenesis appears to be distinct from its canonical cell cyclerelated functions. This finding, implicates Rb-family members for the first time in functions directly related to organ morphogenesis.
lin-35 and
ubc-18 likely act in concert to regulate the levels of one or more critical targets during C. elegans development. Boxem, M. and van den Heuvel, S. (2001).
lin-35 Rb and
cki-1 Cip/Kip cooperate in developmental regulation of G1 progression in C. elegans. Development 128, 4349-59. Fay, D. S., Keenan, S. and Han, M. (2002).
fzr-1 and
lin-35/Rb function redundantly to control cell proliferation in C. elegans as revealed by a nonbiased synthetic screen. Genes Dev 16, 503-17. Lu, X. and Horvitz, H. R. (1998).
lin-35 and
lin-53, two genes that antagonize a C. elegans Ras pathway, encode proteins similar to Rb and its binding protein RbAp48. Cell 95, 981-91.