title: Capicua regulates cell proliferation downstream of the receptor tyrosine kinase/ras signaling pathway.
abstract: Signaling via the receptor tyrosine kinase (RTK)/Ras pathway promotes tissue growth during organismal development and is increased in many cancers [1]. It is still not understood precisely how this pathway promotes cell growth (mass accumulation). In addition, the RTK/Ras pathway also functions in cell survival, cell-fate specification, terminal differentiation, and progression through mitosis [2-7]. An important question is how the same canonical pathway can elicit strikingly different responses in different cell types. Here, we show that the HMG-box protein Capicua (Cic) restricts cell growth in Drosophila imaginal discs, and its levels are, in turn, downregulated by Ras signaling. Moreover, unlike normal cells, the growth of cic mutant cells is undiminished in the complete absence of a Ras signal. In addition to a general role in growth regulation, the importance of cic in regulating cell-fate determination downstream of Ras appears to vary from tissue to tissue. In the developing eye, the analysis of cic mutants shows that the functions of Ras in regulating growth and cell-fate determination are separable. Thus, the DNA-binding protein Cic is a key downstream component in the pathway by which Ras regulates growth in imaginal discs.
authors.affiliation: Massachusetts General Hospital Cancer Center, Charlestown, Massachusetts 02129, USA.
authors.forename: Ai-Sun Kelly
authors.initials: AS
authors.lastname: Tseng
authors.forename: Nicolas
authors.initials: N
authors.lastname: Tapon
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kanda
authors.forename: Seden
authors.initials: S
authors.lastname: Cigizoglu
authors.forename: Lambert
authors.initials: L
authors.lastname: Edelmann
authors.forename: Brett
authors.initials: B
authors.lastname: Pellock
authors.forename: Kristin
authors.initials: K
authors.lastname: White
authors.forename: Iswar K
authors.initials: IK
authors.lastname: Hariharan
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D004330:Drosophila / Q000166:cytology* / Q000254:growth & development / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D005123:Eye / Q000166:cytology / Q000196:embryology / Q000254:growth & development; D024002:HMGB Proteins; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D018631:ras Proteins / Q000378:metabolism*
chemical_list: D029721:Drosophila Proteins; D024002:HMGB Proteins; D012097:Repressor Proteins; C404284:cic protein, Drosophila; D020794:Receptor Protein-Tyrosine Kinases; D018631:ras Proteins