Ubiquitin Degradation of the AICAR Transformylase/IMP Cyclohydrolase Ade16 Regulates the Sexual Reproduction of <i>Cryptococcus neoformans</i>
F-box protein is a key protein of the SCF E3 ubiquitin ligase complex, responsible for substrate recognition and degradation through specific interactions. Previous studies have shown that F-box proteins play crucial roles in <i>Cryptococcus</i> sexual reproduction. However, the molecula...
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MDPI AG
2023-06-01
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| Series: | Journal of Fungi |
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| Online Access: | https://www.mdpi.com/2309-608X/9/7/699 |
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| author | Liantao Han Yujuan Wu Sichu Xiong Tongbao Liu |
| author_facet | Liantao Han Yujuan Wu Sichu Xiong Tongbao Liu |
| author_sort | Liantao Han |
| collection | DOAJ |
| description | F-box protein is a key protein of the SCF E3 ubiquitin ligase complex, responsible for substrate recognition and degradation through specific interactions. Previous studies have shown that F-box proteins play crucial roles in <i>Cryptococcus</i> sexual reproduction. However, the molecular mechanism by which F-box proteins regulate sexual reproduction in <i>C. neoformans</i> is unclear. In the study, we discovered the AICAR transformylase/IMP cyclohydrolase Ade16 as a substrate of Fbp1. Through protein interaction and stability experiments, we demonstrated that Ade16 is a substrate for Fbp1. To examine the role of <i>ADE16</i> in <i>C. neoformans</i>, we constructed the i<i>ADE16</i> strains and <i>ADE16</i><sup>OE</sup> strains to analyze the function of Ade16. Our results revealed that the i<i>ADE16</i> strains had a smaller capsule and showed growth defects under NaCl, while the <i>ADE16</i><sup>OE</sup> strains were sensitive to SDS but not to Congo red, which is consistent with the stress phenotype of the <i>fbp1</i>Δ strains, indicating that the intracellular protein expression level after <i>ADE16</i> overexpression was similar to that after <i>FBP1</i> deletion. Interestingly, although i<i>ADE16</i> strains can produce basidiospores normally, <i>ADE16</i><sup>OE</sup> strains can produce mating mycelia but not basidiospores after mating, which is consistent with the <i>fbp1</i>Δmutant strains, suggesting that Fbp1 is likely to regulate the sexual reproduction of <i>C. neoformans</i> through the modulation of Ade16. A fungal nuclei development assay showed that the nuclei of the <i>ADE16</i><sup>OE</sup> strains failed to fuse in the bilateral mating, indicating that Ade16 plays a crucial role in the regulation of meiosis during mating. In summary, our findings have revealed a new determinant factor involved in fungal development related to the post-translational regulation of AICAR transformylase/IMP cyclohydrolase. |
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| language | English |
| last_indexed | 2024-03-11T00:56:05Z |
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| spelling | doaj.art-ce37eea6e1614361b4935072fab01c6d2023-11-18T20:01:05ZengMDPI AGJournal of Fungi2309-608X2023-06-019769910.3390/jof9070699Ubiquitin Degradation of the AICAR Transformylase/IMP Cyclohydrolase Ade16 Regulates the Sexual Reproduction of <i>Cryptococcus neoformans</i>Liantao Han0Yujuan Wu1Sichu Xiong2Tongbao Liu3State Key Laboratory of Resource Insects, Southwest University Medical Research Institute, Chongqing 400715, ChinaState Key Laboratory of Resource Insects, Southwest University Medical Research Institute, Chongqing 400715, ChinaState Key Laboratory of Resource Insects, Southwest University Medical Research Institute, Chongqing 400715, ChinaState Key Laboratory of Resource Insects, Southwest University Medical Research Institute, Chongqing 400715, ChinaF-box protein is a key protein of the SCF E3 ubiquitin ligase complex, responsible for substrate recognition and degradation through specific interactions. Previous studies have shown that F-box proteins play crucial roles in <i>Cryptococcus</i> sexual reproduction. However, the molecular mechanism by which F-box proteins regulate sexual reproduction in <i>C. neoformans</i> is unclear. In the study, we discovered the AICAR transformylase/IMP cyclohydrolase Ade16 as a substrate of Fbp1. Through protein interaction and stability experiments, we demonstrated that Ade16 is a substrate for Fbp1. To examine the role of <i>ADE16</i> in <i>C. neoformans</i>, we constructed the i<i>ADE16</i> strains and <i>ADE16</i><sup>OE</sup> strains to analyze the function of Ade16. Our results revealed that the i<i>ADE16</i> strains had a smaller capsule and showed growth defects under NaCl, while the <i>ADE16</i><sup>OE</sup> strains were sensitive to SDS but not to Congo red, which is consistent with the stress phenotype of the <i>fbp1</i>Δ strains, indicating that the intracellular protein expression level after <i>ADE16</i> overexpression was similar to that after <i>FBP1</i> deletion. Interestingly, although i<i>ADE16</i> strains can produce basidiospores normally, <i>ADE16</i><sup>OE</sup> strains can produce mating mycelia but not basidiospores after mating, which is consistent with the <i>fbp1</i>Δmutant strains, suggesting that Fbp1 is likely to regulate the sexual reproduction of <i>C. neoformans</i> through the modulation of Ade16. A fungal nuclei development assay showed that the nuclei of the <i>ADE16</i><sup>OE</sup> strains failed to fuse in the bilateral mating, indicating that Ade16 plays a crucial role in the regulation of meiosis during mating. In summary, our findings have revealed a new determinant factor involved in fungal development related to the post-translational regulation of AICAR transformylase/IMP cyclohydrolase.https://www.mdpi.com/2309-608X/9/7/699<i>Cryptococcus neoformans</i>sexual reproductionF-box protein Fbp1AICAR transformylase/IMP cyclohydrolaseAde16 |
| spellingShingle | Liantao Han Yujuan Wu Sichu Xiong Tongbao Liu Ubiquitin Degradation of the AICAR Transformylase/IMP Cyclohydrolase Ade16 Regulates the Sexual Reproduction of <i>Cryptococcus neoformans</i> Journal of Fungi <i>Cryptococcus neoformans</i> sexual reproduction F-box protein Fbp1 AICAR transformylase/IMP cyclohydrolase Ade16 |
| title | Ubiquitin Degradation of the AICAR Transformylase/IMP Cyclohydrolase Ade16 Regulates the Sexual Reproduction of <i>Cryptococcus neoformans</i> |
| title_full | Ubiquitin Degradation of the AICAR Transformylase/IMP Cyclohydrolase Ade16 Regulates the Sexual Reproduction of <i>Cryptococcus neoformans</i> |
| title_fullStr | Ubiquitin Degradation of the AICAR Transformylase/IMP Cyclohydrolase Ade16 Regulates the Sexual Reproduction of <i>Cryptococcus neoformans</i> |
| title_full_unstemmed | Ubiquitin Degradation of the AICAR Transformylase/IMP Cyclohydrolase Ade16 Regulates the Sexual Reproduction of <i>Cryptococcus neoformans</i> |
| title_short | Ubiquitin Degradation of the AICAR Transformylase/IMP Cyclohydrolase Ade16 Regulates the Sexual Reproduction of <i>Cryptococcus neoformans</i> |
| title_sort | ubiquitin degradation of the aicar transformylase imp cyclohydrolase ade16 regulates the sexual reproduction of i cryptococcus neoformans i |
| topic | <i>Cryptococcus neoformans</i> sexual reproduction F-box protein Fbp1 AICAR transformylase/IMP cyclohydrolase Ade16 |
| url | https://www.mdpi.com/2309-608X/9/7/699 |
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