Debra-Mediated Ci Degradation Controls Tissue Homeostasis in Drosophila Adult Midgut

Li, Zhouhua; Guo, Yueqin; Han, Li‐Li; Zhang, Yan; Shi, Lai; Huang, Xiangya; Lin, Xinhua

doi:10.1016/j.stemcr.2013.12.011

Cited by 27 publications

(21 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Considering that SUMO substrates are highly enriched for transcription factors (Hendriks et al, 2014), a likely candidate is Ci, a transcription factor of the Hh pathway (Hui and Angers, 2011;Li et al, 2014;Motzny and Holmgren, 1995). Ci can interact directly with Lwr (Fig.…”

Section: The Sumo Pathway Directly Modifies CImentioning

confidence: 99%

SUMO regulates somatic cyst stem cells maintenance and directly targets hedgehog pathway in adult Drosophila testis

Pan

Zhang

et al. 2016

Development

View full text Add to dashboard Cite

SUMO (Small ubiquitin-related modifier) modification (SUMOylation) is a highly dynamic post-translational modification (PTM) that plays important roles in tissue development and disease progression. However, its function in adult stem cell maintenance is largely unknown. Here, we report the function of SUMOylation in somatic cyst stem cell (CySC) self-renewal in adult Drosophila testis. The SUMO pathway cell-autonomously regulates CySC maintenance. Reduction of SUMOylation promotes premature differentiation of CySCs and impedes the proliferation of CySCs, which leads to a reduction in the number of CySCs. Consistent with this, CySC clones carrying a mutation of the SUMO-conjugating enzyme are rapidly lost. Furthermore, inhibition of the SUMO pathway phenocopies disruption of the Hedgehog (Hh) pathway, and can block the proliferation of CySCs induced by Hh activation. Importantly, the SUMO pathway directly regulates the SUMOylation of Hh pathway transcription factor Cubitus interruptus (Ci), which is required for promoting CySC proliferation. Thus, we conclude that SUMO directly targets the Hh pathway and regulates CySC maintenance in adult Drosophila testis.

show abstract

Section: The Sumo Pathway Directly Modifies CImentioning

confidence: 99%

SUMO regulates somatic cyst stem cells maintenance and directly targets hedgehog pathway in adult Drosophila testis

Pan

Zhang

et al. 2016

Development

View full text Add to dashboard Cite

show abstract

“…Secreted Hedgehog proteins constitute a major family of signaling molecules that guide development, cell proliferation and stem cell behavior in Drosophila and in mammals (Hui and Angers, 2011;Briscoe and Therond, 2013;Zhang and Kalderon, 2001;Peng et al, 2013;Petrova et al, 2013;Li et al, 2014). Accordingly, genetic alterations affecting Hedgehog (Hh) signaling are responsible for a variety of developmental defects and cancers, prompting the development of promising therapeutic drugs (Ng and Curran, 2011;Metcalfe and de Sauvage, 2011;Amakye et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Contributions of Costal 2-Fused interactions to Hedgehog signaling in Drosophila

2015

View full text Add to dashboard Cite

The Drosophila kinesin-family protein Costal 2 (Cos2) and its mammalian ortholog Kif7 play dual roles in Hedgehog (Hh) signaling. In the absence of Hh, Cos2 and Kif7 contribute to proteolytic processing and silencing of the Hh-regulated transcription factors, Drosophila Cubitus interruptus (Ci) and mammalian Gli proteins. Cos2 and Kif7 are also necessary for full activation of full-length Ci-155 and Gli transcription factors in response to Hh proteins. Here, we use classical fused alleles and transgenic Cos2 products deficient for Fused (Fu) association to show that Cos2 must bind to Fu to support efficient Ci-155 processing. Residual Ci-155 processing in the absence of Cos2-Fu interaction did not require Suppressor of Fused, which has been implicated in processing mammalian Gli proteins. We also provide evidence that Cos2 binding to the CORD domain of Ci-155 contributes to both Ci-155 processing and Ci-155 silencing in the absence of Hh. In the presence of Hh, Ci-155 processing is blocked and Cos2 now promotes activation of Ci-155, which requires Fu kinase activity. Here, we show that normal Ci-155 activation by Hh requires Cos2 binding to Fu, supporting the hypothesis that Cos2 mediates the apposition of Fu molecules suitable for cross-phosphorylation and consequent full activation of Fu kinase. We also find that phosphorylation of Cos2 by Fu at two previously mapped sites, S572 and S931, which is thought to mediate Ci-155 activation, is not required for normal activation of Ci-155 by Hh or by activated Fu.

show abstract

“…Both EGFR signaling (Biteau and Jasper, 2011;Buchon et al, 2010;Jiang et al, 2011;Xu et al, 2011) and Hh signaling (Han et al, 2015;Li et al, 2014;Tian et al, 2015) have been shown to promote ISC division during normal midgut homeostasis and regeneration. In addition to the JAK-STAT pathway, we also confirmed the activation of EGFR and Hh signaling in the Sulf1 mutant midgut as follows: (1) upregulation of the vn-lacZ reporter (Yarnitzky et al, 1997) in visceral muscles (Fig.…”

Section: P1mentioning

confidence: 99%

“…It has been shown that ISC division and differentiation are regulated by several signaling pathways, including Janus kinase and signal transducer and activator of transcription (JAK-STAT), epidermal growth factor receptor (EGFR), Hedgehog (Hh), bone morphogenetic protein (BMP) and Wingless (Wg) signaling (Ayyaz et al, 2015;Beebe et al, 2010;Biteau and Jasper, 2011;Buchon et al, 2009aBuchon et al, ,b, 2010Cordero et al, 2007Cordero et al, , 2012Cronin et al, 2009;Guo et al, 2013;Jiang et al, 2009Jiang et al, , 2011Lee et al, 2009;Li et al, 2014Li et al, , 2013bLin et al, 2008Lin et al, , 2010Liu et al, 2010;Osman et al, 2013;Tian and Jiang, 2014;Tian et al, 2015;Xu et al, 2011;Zhou et al, 2013Zhou et al, , 2015. In response to tissue damage, the ligands of these pathways are transcriptionally upregulated in cells surrounding ISCs, and activate signal transduction in ISCs to promote their division.…”

Section: Introductionmentioning

confidence: 99%

Drosophila Sulf1 is required for the termination of intestinal stem cell division during regeneration

Takemura

Nakato

2017

Journal of Cell Science

View full text Add to dashboard Cite

Stem cell division is activated to trigger regeneration in response to tissue damage. The molecular mechanisms by which this stem cell mitotic activity is properly repressed at the end of regeneration are poorly understood. Here, we show that a specific modification of heparan sulfate is crucial for regulating Drosophila intestinal stem cell (ISC) division during normal midgut homeostasis and regeneration. Loss of the extracellular heparan sulfate endosulfatase Sulf1 resulted in increased ISC division during normal homeostasis, which was caused by upregulation of mitogenic signaling including the JAK-STAT, EGFR and Hedgehog pathways. Using a regeneration model, we found that ISCs failed to properly halt division at the termination stage in Sulf1 mutants, showing that Sulf1 is required for terminating ISC division at the end of regeneration. We propose that posttranscriptional regulation of mitogen signaling by heparan sulfate structural modifications provides a new regulatory step for precise temporal control of stem cell activity during regeneration.

show abstract

Debra-Mediated Ci Degradation Controls Tissue Homeostasis in Drosophila Adult Midgut

Cited by 27 publications

References 44 publications

SUMO regulates somatic cyst stem cells maintenance and directly targets hedgehog pathway in adult Drosophila testis

SUMO regulates somatic cyst stem cells maintenance and directly targets hedgehog pathway in adult Drosophila testis

Contributions of Costal 2-Fused interactions to Hedgehog signaling in Drosophila

Drosophila Sulf1 is required for the termination of intestinal stem cell division during regeneration

Contact Info

Product

Resources

About