lin 35


Gene Symbol: lin 35
Description: Retinoblastoma-like protein homolog lin-35
Alias: Retinoblastoma-like protein homolog lin-35
Species: Caenorhabditis elegans

Top Publications

  1. Davison E, Harrison M, Walhout A, Vidal M, Horvitz H. lin-8, which antagonizes Caenorhabditis elegans Ras-mediated vulval induction, encodes a novel nuclear protein that interacts with the LIN-35 Rb protein. Genetics. 2005;171:1017-31 pubmed
  2. Lu X, Horvitz H. 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. 1998;95:981-91 pubmed
    ..We propose that LIN-35 and LIN-53 antagonize the Ras signaling pathway in C. elegans by repressing transcription in the vulval precursor cells of genes required for the expression of vulval cell fates. ..
  3. Fay D, Large E, Han M, Darland M. lin-35/Rb and ubc-18, an E2 ubiquitin-conjugating enzyme, function redundantly to control pharyngeal morphogenesis in C. elegans. Development. 2003;130:3319-30 pubmed
    ..lin-35 and ubc-18 may act in concert to regulate the levels of one or more critical targets during C. elegans development...
  4. Lehner B, Calixto A, Crombie C, Tischler J, Fortunato A, Chalfie M, et al. Loss of LIN-35, the Caenorhabditis elegans ortholog of the tumor suppressor p105Rb, results in enhanced RNA interference. Genome Biol. 2006;7:R4 pubmed
    ..As lin-35 is the worm ortholog of the mammalian tumor suppressor gene p105Rb, misregulation of RNAi may be important during human oncogenesis. ..
  5. Boxem M, van den Heuvel S. lin-35 Rb and cki-1 Cip/Kip cooperate in developmental regulation of G1 progression in C. elegans. Development. 2001;128:4349-59 pubmed
    ..Surprisingly, loss of cki-1, but not lin-35, results in precocious entry into S phase. We suggest that a rate limiting role for cki-1 Cip/Kip rather than lin-35 Rb explains the lack of cell-cycle phenotype of lin-35 mutant animals. ..
  6. Petrella L, Wang W, Spike C, Rechtsteiner A, Reinke V, Strome S. synMuv B proteins antagonize germline fate in the intestine and ensure C. elegans survival. Development. 2011;138:1069-79 pubmed publisher
    ..Somatic expression of germline genes is enhanced at elevated temperature, leading to developmentally compromised somatic cells and arrest of newly hatched larvae. ..
  7. Bender A, Kirienko N, Olson S, Esko J, Fay D. lin-35/Rb and the CoREST ortholog spr-1 coordinately regulate vulval morphogenesis and gonad development in C. elegans. Dev Biol. 2007;302:448-62 pubmed
    ..This defect, which is observed in lin-35; spr-1; lin-12(RNAi) and lin-35; spr-1; hop-1(RNAi) triple mutants is likely due to a delay in the entry of germ cells into meiosis. ..
  8. Fay D, Qiu X, Large E, Smith C, Mango S, Johanson B. The coordinate regulation of pharyngeal development in C. elegans by lin-35/Rb, pha-1, and ubc-18. Dev Biol. 2004;271:11-25 pubmed
  9. Schertel C, Conradt B. C. elegans orthologs of components of the RB tumor suppressor complex have distinct pro-apoptotic functions. Development. 2007;134:3691-701 pubmed
    ..Our results have implications for the general mechanisms through which RB-like proteins control gene expression, the role of RB-, DP- and E2F-like proteins in apoptosis, and the regulation of apoptosis. ..

More Information


  1. Cui M, Fay D, Han M. lin-35/Rb cooperates with the SWI/SNF complex to control Caenorhabditis elegans larval development. Genetics. 2004;167:1177-85 pubmed
    ..Our results suggest that LIN-35/Rb and a certain class B synMuv proteins collaborate with the SWI/SNF protein complex to regulate the T cell division as well as other events essential for larval growth...
  2. Bender A, Wells O, Fay D. lin-35/Rb and xnp-1/ATR-X function redundantly to control somatic gonad development in C. elegans. Dev Biol. 2004;273:335-49 pubmed
    ..elegans. In addition, our results suggest a possible conserved function for xnp-1/ATR-X in gonadal development across species. ..
  3. Reddien P, Andersen E, Huang M, Horvitz H. DPL-1 DP, LIN-35 Rb and EFL-1 E2F act with the MCD-1 zinc-finger protein to promote programmed cell death in Caenorhabditis elegans. Genetics. 2007;175:1719-33 pubmed
    ..We propose that the DPL-1 DP, MCD-1 zinc finger, EFL-1 E2F, LIN-35 Rb, LIN-37 Mip40, and LIN-52 dLin52 proteins act together in transcriptional regulation to promote programmed cell death. ..
  4. Poulin G, Dong Y, Fraser A, Hopper N, Ahringer J. Chromatin regulation and sumoylation in the inhibition of Ras-induced vulval development in Caenorhabditis elegans. EMBO J. 2005;24:2613-23 pubmed
    ..As most of the genes identified in this screen are conserved in humans, we suggest that similar interactions may be relevant in mammals for control of Ras and Notch signalling, crosstalk between these pathways, and cell proliferation...
  5. Voutev R, Killian D, Ahn J, Hubbard E. Alterations in ribosome biogenesis cause specific defects in C. elegans hermaphrodite gonadogenesis. Dev Biol. 2006;298:45-58 pubmed
    ..We conclude that the C. elegans distal sheath is particularly sensitive to alterations in ribosome biogenesis and that ribosome biogenesis defects in one tissue can non-autonomously influence proliferation in an adjacent tissue. ..
  6. Ceol C, Horvitz H. dpl-1 DP and efl-1 E2F act with lin-35 Rb to antagonize Ras signaling in C. elegans vulval development. Mol Cell. 2001;7:461-73 pubmed
    ..We propose that rather than being inhibited by lin-35 Rb, dpl-1 DP and efl-1 E2F act with lin-35 Rb in transcriptional repression to antagonize RTK/Ras signaling during vulval development. ..
  7. Coustham V, Bedet C, Monier K, Schott S, Karali M, Palladino F. The C. elegans HP1 homologue HPL-2 and the LIN-13 zinc finger protein form a complex implicated in vulval development. Dev Biol. 2006;297:308-22 pubmed
    ..We further show by in vivo localization studies that LIN-13 is required for HPL-2 recruitment in nuclear foci. Our data suggest that the LIN-13/HPL-2 complex may physically link a subset of the Rb related synMuv proteins to chromatin. ..
  8. Myers T, Greenwald I. lin-35 Rb acts in the major hypodermis to oppose ras-mediated vulval induction in C. elegans. Dev Cell. 2005;8:117-23 pubmed
    ..LIN-35 Rb may inhibit vulval fates by regulating a signal from hyp7 to the VPCs or the physiological state of hyp7. ..
  9. Grishok A, Sharp P. Negative regulation of nuclear divisions in Caenorhabditis elegans by retinoblastoma and RNA interference-related genes. Proc Natl Acad Sci U S A. 2005;102:17360-5 pubmed
    ..We propose that RNA interference-related pathways cooperate with retinoblastoma in transcriptional repression of endogenous genes, an example being cyclin E. ..
  10. Kirienko N, McEnerney J, Fay D. Coordinated regulation of intestinal functions in C. elegans by LIN-35/Rb and SLR-2. PLoS Genet. 2008;4:e1000059 pubmed publisher
    ..Our studies also shed light on the mechanistic basis of genetic redundancy among transcriptional regulators and suggest that synthetic interactions may result from the synergistic misregulation of one or more common targets. ..
  11. Tilmann C, Kimble J. Cyclin D regulation of a sexually dimorphic asymmetric cell division. Dev Cell. 2005;9:489-99 pubmed
    ..We propose that cyclin D and other canonical regulators of the G1/S transition coordinate key regulators of axis formation and sex determination with cell cycle progression to achieve the sexually dimorphic SGP asymmetric division. ..
  12. Garbe D, Doto J, Sundaram M. Caenorhabditis elegans lin-35/Rb, efl-1/E2F and other synthetic multivulva genes negatively regulate the anaphase-promoting complex gene mat-3/APC8. Genetics. 2004;167:663-72 pubmed
    ..Loss-of-function alleles of lin-35/Rb and other SynMuv B genes suppress mat-3(ku233) defects by restoring mat-3 mRNA to wild-type levels. Therefore, Rb/E2F complexes appear to repress mat-3 expression. ..
  13. Goetsch P, Garrigues J, Strome S. Loss of the Caenorhabditis elegans pocket protein LIN-35 reveals MuvB's innate function as the repressor of DREAM target genes. PLoS Genet. 2017;13:e1007088 pubmed publisher
    ..Our findings provide important insights into how mammalian DREAM assembly and disassembly may regulate gene expression and the cell cycle. ..
  14. Massirer K, Perez S, Mondol V, Pasquinelli A. The miR-35-41 family of microRNAs regulates RNAi sensitivity in Caenorhabditis elegans. PLoS Genet. 2012;8:e1002536 pubmed publisher
    ..Our results reveal that miRNAs can broadly regulate other small RNA pathways and, thus, have far reaching effects on gene expression beyond directly targeting specific mRNAs. ..
  15. Cui M, Cohen M, Teng C, Han M. The tumor suppressor Rb critically regulates starvation-induced stress response in C. elegans. Curr Biol. 2013;23:975-80 pubmed publisher
    ..These results may provide mechanistic insights into why cancer cells are often hypersensitive to starvation treatment. ..
  16. Schott S, Coustham V, Simonet T, Bedet C, Palladino F. Unique and redundant functions of C. elegans HP1 proteins in post-embryonic development. Dev Biol. 2006;298:176-87 pubmed
    ..However, HPL-1 and HPL-2 localization does not completely overlap. Our results show that HPL-1 and HPL-2 play both unique and redundant functions in post-embryonic development. ..
  17. Wu X, Shi Z, Cui M, Han M, Ruvkun G. Repression of germline RNAi pathways in somatic cells by retinoblastoma pathway chromatin complexes. PLoS Genet. 2012;8:e1002542 pubmed publisher
    ..Regulation of small RNA pathway genes by human retinoblastoma may also underlie its role as a tumor suppressor gene. ..
  18. Láscarez Lagunas L, Silva García C, Dinkova T, Navarro R. LIN-35/Rb causes starvation-induced germ cell apoptosis via CED-9/Bcl2 downregulation in Caenorhabditis elegans. Mol Cell Biol. 2014;34:2499-516 pubmed publisher
    ..We propose that CED-9/Bcl-2 downregulation via LIN-35/Rb triggers germ cell apoptosis in C. elegans in response to starvation. ..
  19. Ouellet J, Roy R. The lin-35/Rb and RNAi pathways cooperate to regulate a key cell cycle transition in C. elegans. BMC Dev Biol. 2007;7:38 pubmed
    ..The lin-35/Rb repressor complex may be required to initiate this process, while components of the RNAi machinery positively reinforce this repression. ..
  20. Saito R, Perreault A, Peach B, Satterlee J, van den Heuvel S. The CDC-14 phosphatase controls developmental cell-cycle arrest in C. elegans. Nat Cell Biol. 2004;6:777-83 pubmed
    ..Our data support a model in which CDC-14 promotes a hypophosphorylated and stable form of CKI-1 required for developmentally programmed cell-cycle arrest. ..
  21. Mani K, Fay D. A mechanistic basis for the coordinated regulation of pharyngeal morphogenesis in Caenorhabditis elegans by LIN-35/Rb and UBC-18-ARI-1. PLoS Genet. 2009;5:e1000510 pubmed publisher
    ..Our results also shed light on general mechanisms that may underlie developmental genetic redundancies as well as principles that may govern complex disease traits. ..
  22. The I, Ruijtenberg S, Bouchet B, Cristobal A, Prinsen M, van Mourik T, et al. Rb and FZR1/Cdh1 determine CDK4/6-cyclin D requirement in C. elegans and human cancer cells. Nat Commun. 2015;6:5906 pubmed publisher
    ..Our data identify FZR1 as a candidate CDK4/6-cyclin D substrate and point to an APC/C(FZR1) activity as an important determinant in response to CDK4/6-inhibitors. ..