The E23 early gene of Drosophila encodes an ecdysone-inducible ATP-binding cassette transporter capable of repressing ecdysone-mediated gene activation

Abstract

At the onset of Drosophila metamorphosis, the steroid hormone 20-OH ecdysone directly induces a small number of early puffs in the polytene chromosomes of the larval salivary gland. Proteins encoded by the early genes corresponding to these transcriptional puffs then regulate the activity of both the early puffs themselves and a much larger set of late puffs. Three of these early genes encode transcription factors that play critical regulatory roles during metamorphosis. Here we report the cloning, DNA sequence, genomic structure, ecdysone inducibility, and temporal expression of an early gene residing in the 23E early puff and denoted E23 (Early gene at 23). In contrast to other early genes, E23 encodes a protein with similarity to ATP-binding cassette transporters. Using heat shock-inducible transgenes, we found that E23 overexpression not only produces phenotypic abnormalities and lethality, but also interferes with ecdysone-mediated gene activation, demonstrating that E23 is capable of modulating the ecdysone response. Our results suggest the existence of a previously unrecognized regulatory mechanism for modulating steroid hormone signaling in Drosophila.

Ecdysone Control of Developmental Transitions: Lessons from Drosophila Research

“…One mechanism involves the ecdysone-inducible ATP-binding cassette transporter E23, which has been suggested to pump ecdysone out of the cell to lower its cytoplasmic concentration (43). Another example is Cyp18a1, which is an ecdysone-metabolizing cytochrome P450 whose expression is induced by ecdysone (39, 46, 97).…”

Developmental Checkpoints and Feedback Circuits Time Insect Maturation

“…In addition to metabolic inactivation, another mechanism ensures that cellular levels of ecdysone are reduced following a peak. One of the early ecdysone-inducible genes, E23 , encodes an ABC transporter protein (Hock, Cottrill, Keegan, & Garza, 2000). E23 is one of the last of the early genes to be induced which makes physiological sense because the function of E23 is to pump ecdysone out of the cells and reduce cellular concentration.…”

The molecular mechanisms of cuticular melanization: The ecdysone cascade leading to dopa decarboxylase expression in Manduca sexta

“…Many of the genes activated early are transcription factors, but the early puff gene E63-1 encodes a calcium-binding protein, most closely related to calmodulin (Vaskova et al, 2000); E63-1 is responsible for glue secretion from the salivary gland (Biyasheva et al, 2001). Another early puff gene E23 encodes a member of the ABC family of transporter proteins that may remove ecdysone from the cell, raising new possibilities for the understanding of the regulation of ecdysone responses (Hock et al, 2000).…”