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Bunched, the Drosophila homolog of the mammalian tumor suppressor TSC-22, promotes cellular growth

DOI: 10.1186/1471-213x-8-10

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We have identified bun in an unbiased genetic screen for growth regulators in Drosophila. Rather unexpectedly, bun mutations result in a growth deficit. Under standard conditions, only the long protein isoform BunA – but not the short isoforms BunB and BunC – is essential and affects growth. Whereas reducing bunA function diminishes cell number and cell size, overexpression of the short isoforms BunB and BunC antagonizes bunA function.Our findings establish a growth-promoting function of Drosophila BunA. Since the published studies on mammalian systems have largely neglected the long TSC-22 protein version, we hypothesize that the long TSC-22 protein is a functional homolog of BunA in growth regulation, and that it is antagonized by the short TSC-22 protein.Tumorigenesis is frequently associated with a loss of a tumor suppressor, allowing tumor cells to become self-sufficient in growth signals, to become insensitive to growth-inhibitory signals, or to evade apoptosis (reviewed in [1]). Thus, the functional characterization of tumor suppressors is key to a better understanding of the signaling events leading to aberrant growth.Transforming Growth Factor-β1 stimulated clone-22 (TSC-22) is a putative negative growth regulator and tumor suppressor in mammals. TSC-22 has first been isolated as a TGF-β1 responsive gene from a mouse osteoblastic cell line [2]. It encodes a putative transcription factor that binds to DNA in vitro via its TSC-box [3]. TSC-22 expression has been found to be lowered in different mouse and human tumors, including liver [4], brain [5], prostate [6], and salivary gland tumors [7]. Consistently, downregulation of TSC-22 enhances growth in the salivary gland cell line TYS [7], whereas upregulation of TSC-22 is associated with apoptosis [8,9] and growth inhibition [10]. Increased TSC-22 expression also correlates with growth inhibition in primary human prostatic cancer cells [11,12]. Furthermore, in the mammary carcinoma cell line T47D, TSC-22 is a

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