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Suppressor of fused and Spop regulate the stability, processing and function of Gli2 and Gli3 full-length activators but not their repressors.

ABSTRACT: Gli2 and Gli3 are primary transcriptional regulators that mediate hedgehog (Hh) signaling. Mechanisms that stabilize and destabilize Gli2 and Gli3 are essential for the proteins to promptly respond to Hh signaling or to be inactivated following the activation. In this study, we show that loss of suppressor of fused (Sufu; an inhibitory effector for Gli proteins) results in destabilization of Gli2 and Gli3 full-length activators but not of their C-terminally processed repressors, whereas overexpression of Sufu stabilizes them. By contrast, RNAi knockdown of Spop (a substrate-binding adaptor for the cullin3-based ubiquitin E3 ligase) in Sufu mutant mouse embryonic fibroblasts (MEFs) can restore the levels of Gli2 and Gli3 full-length proteins, but not those of their repressors, whereas introducing Sufu into the MEFs stabilizes Gli2 and Gli3 full-length proteins and rescues Gli3 processing. Consistent with these findings, forced Spop expression promotes Gli2 and Gli3 degradation and Gli3 processing. The functions of Sufu and Spop oppose each other through their competitive binding to the N- and C-terminal regions of Gli3 or the C-terminal region of Gli2. More importantly, the Gli3 repressor expressed by a Gli3 mutant allele (Gli3(Delta699)) can mostly rescue the ventralized neural tube phenotypes of Sufu mutant embryos, indicating that the Gli3 repressor can function independently of Sufu. Our study provides a new insight into the regulation of Gli2 and Gli3 stability and processing by Sufu and Spop, and reveals the unexpected Sufu-independent Gli3 repressor function.

SUBMITTER: Wang C

PROVIDER: S-EPMC2875842 | biostudies-other | 2010 Jun

REPOSITORIES: biostudies-other

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Suppressor of fused and Spop regulate the stability, processing and function of Gli2 and Gli3 full-length activators but not their repressors.

Wang Chengbing C Pan Yong Y Wang Baolin B

Development (Cambridge, England) 20100512 12

Gli2 and Gli3 are primary transcriptional regulators that mediate hedgehog (Hh) signaling. Mechanisms that stabilize and destabilize Gli2 and Gli3 are essential for the proteins to promptly respond to Hh signaling or to be inactivated following the activation. In this study, we show that loss of suppressor of fused (Sufu; an inhibitory effector for Gli proteins) results in destabilization of Gli2 and Gli3 full-length activators but not of their C-terminally processed repressors, whereas overexpr ...[more]

PMID: 20463034

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Project description:Juvenile red fading describes the phenomenon in plants whereby red young leaves gradually turn green as they mature. While this phenomenon is commonly observed, the underlying molecular mechanism is still obscure as the classic model plants do not exhibit this process. Here, the molecular mechanism for the loss of anthocyanins during juvenile red fading were explored in the sweetpotato (Ipomoea batatas L.) cultivar "Chuanshan Zi". The MYB-bHLH-WDR (MBW) regulatory complexes for anthocyanins were examined with five stages of leaf development from C1 to C5. Alternating accumulation of anthocyanins and chlorophylls caused the leaf color change. Five anthocyanin components were identified by ultra performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS), and their contents were highest at stage C2. Transcriptomic analysis showed massive gene expression alteration during leaf development. The anthocyanin structural genes expressed in sweetpotato leaves were screened and found to be highly comparable with those identified in morning glories. The screened anthocyanin regulatory genes included one bHLH (IbbHLH2), one WDR (IbWDR1), three MYB activators (IbMYB1, IbMYB2, and IbMYB3), and five MYB repressors (IbMYB27, IbMYBx, IbMYB4a, IbMYB4b, and IbMYB4c). The expression trends of MYBs were key to the red fading process: the activators were highly expressed in early red leaves and were all accompanied by simultaneously expressed MYB repressors, which may act to prevent excessive accumulation of anthocyanins. The only antagonistic repressor, IbMYB4b, was highly expressed in green leaves, and may be critical for declined anthocyanin content at later stages. Further functional verification of the above transcription factors were conducted by promoter activation tests. These tests showed that the MBW complexes of IbMYB1/IbMYB2/IbMYB3-IbbHLH2-IbWDR1 not only activated promoters of anthocyanin structural genes IbCHS-D and IbDFR-B, but also promoters for IbbHLH2 and IbMYB27, indicating both hierarchical and feedback regulations. This study outlines the elaborate regulatory network of MBW complexes involving multiple MYBs which allow for the timely accumulation of anthocyanins in sweetpotato leaves. These results may also provide clues for similar studies of juvenile red fading in other plant species.

Dataset Information

Suppressor of fused and Spop regulate the stability, processing and function of Gli2 and Gli3 full-length activators but not their repressors.

Publications

Suppressor of fused and Spop regulate the stability, processing and function of Gli2 and Gli3 full-length activators but not their repressors.

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