The Drosophila casein kinase Iε/δ Discs overgrown promotes cell survival via activation of DIAP1 expression

Abstract

The proper number of cells in developing tissues is achieved by coordinating cell division with apoptosis. In Drosophila, the adult wing is derived from wing imaginal discs, which undergo a period of growth and proliferation during larval stages without much programmed cell death. In this report, we demonstrate that the Drosophila casein kinase Iepsilon/delta, known as Discs overgrown (Dco), is required for maintaining this low level of apoptosis. Expression of dco can suppress the apoptotic activity of Head involution defective (Hid) in the developing eye. Loss of dco in the wing disc results in a dramatic reduction in expression of the caspase inhibitor DIAP1 and a concomitant activation of caspases. The regulation of DIAP1 by Dco occurs by a post-transcriptional mechanism that is independent of hid. Mutant clones of dco are considerably smaller than controls even when apoptosis is inhibited, suggesting that Dco promotes cell division/growth in addition to its role in cell survival. The dco phenotype cannot be explained by defects Wingless (Wg) signaling. We propose that Dco coordinates tissue size by stimulating cell division/growth and blocking apoptosis via activation of DIAP1 expression.

Processing and phosphorylation of the Fat receptor

“…This could reflect the participation of dco in other processes. However, targets of Fat signaling, including Wingless (WG) in the proximal wing, and Diap1, are up-regulated in dco 3 mutant clones (11), but not in dco null (dco le88 ) mutant clones (6). The apparent absence of fat phenotypes in dco null alleles suggests that dco 3 is an unusual allele.…”

Casein kinase I epsilon somatic mutations found in breast cancer cause overgrowth in Drosophila

“…For example the Dco 3 mutant protein phosphorylates the circadian rhythm protein Period normally but shows altered phosphorylation of the Fat receptor, while Dco Dbt-AR shows altered Period phosphorylation (Feng and Irvine 2009). The normal function of Dco must be required for tissue growth, since the null mutant larvae are discless due to the reduction of apoptosis inhibitor DIAP1 (Guan et al 2007). One possible mechanism could be that Dco fine-tunes the Fat/Warts inhibitory pathway via Fat phosphorylation (Fig.…”

“…4A). Null dco mutants, which lack this function, exhibit a reduction of DIAP1 (Guan et al 2007), one of the Fat/Warts signaling targets. Furthermore, dco L39Q like dco 3 could then lead to excessive inhibition of Fat/Warts signaling, via aberrant Fat phosphorylation, resulting in excessive tissue growth (Fig.…”

Drosophila ptipis essential for anterior/posterior patterning in development and interacts with the PcG and trxG pathways

“…Zygotic ptip mutant wing imaginal discs and salivary glands were prepared from PBac ptip /Df(ptip) 1 third instar larvae and immunostained as described (Guan et al, 2007;Parker et al, 2002). Rabbit anti-DLL (1:200) was from J. Kohtz (Northwestern University, Chicago, IL, USA), monoclonal anti-EN (1:20) and anti-WG (1:100) were from the Developmental Studies Hybridoma Bank (Iowa City, IA, USA), rabbit antiHistone H3 (trimethyl K4, 1:200) and anti-Histone H3 (trimethyl K27, 1:200) were ChIP grade and purchased from Abcam (Cambridge, UK).…”