The Candida albicans Cdk8-dependent phosphoproteome reveals repression of hyphal growth through a Flo8-dependent pathway Article Swipe
Jeffrey M. Hollomon
,
Zhongle Liu
,
Scott Rusin
,
Nicole P. Jenkins
,
Allia K. Smith
,
Katja Koeppen
,
Arminja N. Kettenbach
,
Lawrence C. Myers
,
Deborah A. Hogan
·
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.1371/journal.pgen.1009622
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.1371/journal.pgen.1009622
Ssn3, also known as Cdk8, is a member of the four protein Cdk8 submodule within the multi-subunit Mediator complex involved in the co-regulation of transcription. In Candida albicans , the loss of Ssn3 kinase activity affects multiple phenotypes including cellular morphology, metabolism, nutrient acquisition, immune cell interactions, and drug resistance. In these studies, we generated a strain in which Ssn3 was replaced with a functional variant of Ssn3 that can be rapidly and selectively inhibited by the ATP analog 3-MB-PP1. Consistent with ssn3 null mutant and kinase dead phenotypes, inhibition of Ssn3 kinase activity promoted hypha formation. Furthermore, the increased expression of hypha-specific genes was the strongest transcriptional signal upon inhibition of Ssn3 in transcriptomics analyses. Rapid inactivation of Ssn3 was used for phosphoproteomic studies performed to identify Ssn3 kinase substrates associated with filamentation potential. Both previously validated and novel Ssn3 targets were identified. Protein phosphorylation sites that were reduced specifically upon Ssn3 inhibition included two sites in Flo8 which is a transcription factor known to positively regulate C . albicans morphology. Mutation of the two Flo8 phosphosites (threonine 589 and serine 620) was sufficient to increase Flo8-HA levels and Flo8 dependent transcriptional and morphological changes, suggesting that Ssn3 kinase activity negatively regulates Flo8.Under embedded conditions, when ssn3 Δ/Δ and efg1 Δ/Δ mutants were hyperfilamentous, FLO8 was essential for hypha formation. Previous work has also shown that loss of Ssn3 activity leads to increased alkalinization of medium with amino acids. Here, we show that the ssn3 Δ/Δ medium alkalinization phenotype, which is dependent on STP2 , a transcription factor involved in amino acid utilization, also requires FLO8 and EFG1 . Together, these data show that Ssn3 activity can modulate Flo8 and its direct and indirect interactions in different ways, and underscores the potential importance of considering Ssn3 function in the control of transcription factor activities.
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Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1371/journal.pgen.1009622
- OA Status
- gold
- Cited By
- 13
- References
- 63
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4221034436
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4221034436Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1371/journal.pgen.1009622Digital Object Identifier
- Title
-
The Candida albicans Cdk8-dependent phosphoproteome reveals repression of hyphal growth through a Flo8-dependent pathwayWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2022Year of publication
- Publication date
-
2022-01-04Full publication date if available
- Authors
-
Jeffrey M. Hollomon, Zhongle Liu, Scott Rusin, Nicole P. Jenkins, Allia K. Smith, Katja Koeppen, Arminja N. Kettenbach, Lawrence C. Myers, Deborah A. HoganList of authors in order
- Landing page
-
https://doi.org/10.1371/journal.pgen.1009622Publisher landing page
- Open access
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YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
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https://doi.org/10.1371/journal.pgen.1009622Direct OA link when available
- Concepts
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Biology, Candida albicans, Kinase, Cell biology, Cyclin-dependent kinase 8, Transcription factor, Protein kinase A, Mutant, Corpus albicans, Signal transduction, Biochemistry, Genetics, Gene, Notch signaling pathwayTop concepts (fields/topics) attached by OpenAlex
- Cited by
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13Total citation count in OpenAlex
- Citations by year (recent)
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2025: 3, 2024: 2, 2023: 7, 2022: 1Per-year citation counts (last 5 years)
- References (count)
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63Number of works referenced by this work
- Related works (count)
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10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.on | 253 |
| abstract_inverted_index.to | 126, 165, 185, 232 |
| abstract_inverted_index.we | 53, 241 |
| abstract_inverted_index.589 | 179 |
| abstract_inverted_index.ATP | 77 |
| abstract_inverted_index.and | 47, 72, 85, 138, 180, 189, 193, 209, 267, 280, 283, 289 |
| abstract_inverted_index.can | 69, 277 |
| abstract_inverted_index.for | 122, 218 |
| abstract_inverted_index.has | 223 |
| abstract_inverted_index.its | 281 |
| abstract_inverted_index.the | 9, 15, 21, 29, 76, 98, 105, 174, 244, 291, 299 |
| abstract_inverted_index.two | 155, 175 |
| abstract_inverted_index.was | 60, 104, 120, 183, 216 |
| abstract_inverted_index.620) | 182 |
| abstract_inverted_index.Both | 135 |
| abstract_inverted_index.Cdk8 | 12 |
| abstract_inverted_index.EFG1 | 268 |
| abstract_inverted_index.FLO8 | 215, 266 |
| abstract_inverted_index.Flo8 | 158, 176, 190, 279 |
| abstract_inverted_index.STP2 | 254 |
| abstract_inverted_index.Ssn3 | 32, 59, 67, 91, 112, 119, 128, 140, 152, 198, 229, 275, 296 |
| abstract_inverted_index.acid | 262 |
| abstract_inverted_index.also | 1, 224, 264 |
| abstract_inverted_index.cell | 45 |
| abstract_inverted_index.data | 272 |
| abstract_inverted_index.dead | 87 |
| abstract_inverted_index.drug | 48 |
| abstract_inverted_index.efg1 | 210 |
| abstract_inverted_index.four | 10 |
| abstract_inverted_index.loss | 30, 227 |
| abstract_inverted_index.null | 83 |
| abstract_inverted_index.show | 242, 273 |
| abstract_inverted_index.ssn3 | 82, 207, 245 |
| abstract_inverted_index.that | 68, 147, 197, 226, 243, 274 |
| abstract_inverted_index.upon | 109, 151 |
| abstract_inverted_index.used | 121 |
| abstract_inverted_index.were | 142, 148, 213 |
| abstract_inverted_index.when | 206 |
| abstract_inverted_index.with | 62, 81, 132, 237 |
| abstract_inverted_index.work | 222 |
| abstract_inverted_index.Cdk8, | 4 |
| abstract_inverted_index.Here, | 240 |
| abstract_inverted_index.Rapid | 116 |
| abstract_inverted_index.Ssn3, | 0 |
| abstract_inverted_index.amino | 238, 261 |
| abstract_inverted_index.genes | 103 |
| abstract_inverted_index.hypha | 95, 219 |
| abstract_inverted_index.known | 2, 164 |
| abstract_inverted_index.leads | 231 |
| abstract_inverted_index.novel | 139 |
| abstract_inverted_index.shown | 225 |
| abstract_inverted_index.sites | 146, 156 |
| abstract_inverted_index.these | 51, 271 |
| abstract_inverted_index.ways, | 288 |
| abstract_inverted_index.which | 58, 159, 250 |
| abstract_inverted_index.Δ/Δ | 208, 211, 246 |
| abstract_inverted_index.acids. | 239 |
| abstract_inverted_index.analog | 78 |
| abstract_inverted_index.direct | 282 |
| abstract_inverted_index.factor | 163, 258, 303 |
| abstract_inverted_index.immune | 44 |
| abstract_inverted_index.kinase | 33, 86, 92, 129, 199 |
| abstract_inverted_index.levels | 188 |
| abstract_inverted_index.medium | 236, 247 |
| abstract_inverted_index.member | 7 |
| abstract_inverted_index.mutant | 84 |
| abstract_inverted_index.serine | 181 |
| abstract_inverted_index.signal | 108 |
| abstract_inverted_index.strain | 56 |
| abstract_inverted_index.within | 14 |
| abstract_inverted_index.Candida | 26 |
| abstract_inverted_index.Flo8-HA | 187 |
| abstract_inverted_index.Protein | 144 |
| abstract_inverted_index.affects | 35 |
| abstract_inverted_index.complex | 18 |
| abstract_inverted_index.control | 300 |
| abstract_inverted_index.mutants | 212 |
| abstract_inverted_index.protein | 11 |
| abstract_inverted_index.rapidly | 71 |
| abstract_inverted_index.reduced | 149 |
| abstract_inverted_index.studies | 124 |
| abstract_inverted_index.targets | 141 |
| abstract_inverted_index.variant | 65 |
| abstract_inverted_index.Mediator | 17 |
| abstract_inverted_index.Mutation | 172 |
| abstract_inverted_index.Previous | 221 |
| abstract_inverted_index.activity | 34, 93, 200, 230, 276 |
| abstract_inverted_index.albicans | 27, 170 |
| abstract_inverted_index.cellular | 39 |
| abstract_inverted_index.changes, | 195 |
| abstract_inverted_index.embedded | 204 |
| abstract_inverted_index.function | 297 |
| abstract_inverted_index.identify | 127 |
| abstract_inverted_index.included | 154 |
| abstract_inverted_index.increase | 186 |
| abstract_inverted_index.indirect | 284 |
| abstract_inverted_index.involved | 19, 259 |
| abstract_inverted_index.modulate | 278 |
| abstract_inverted_index.multiple | 36 |
| abstract_inverted_index.nutrient | 42 |
| abstract_inverted_index.promoted | 94 |
| abstract_inverted_index.regulate | 167 |
| abstract_inverted_index.replaced | 61 |
| abstract_inverted_index.requires | 265 |
| abstract_inverted_index.studies, | 52 |
| abstract_inverted_index.3-MB-PP1. | 79 |
| abstract_inverted_index.Together, | 270 |
| abstract_inverted_index.analyses. | 115 |
| abstract_inverted_index.dependent | 191, 252 |
| abstract_inverted_index.different | 287 |
| abstract_inverted_index.essential | 217 |
| abstract_inverted_index.generated | 54 |
| abstract_inverted_index.including | 38 |
| abstract_inverted_index.increased | 99, 233 |
| abstract_inverted_index.inhibited | 74 |
| abstract_inverted_index.performed | 125 |
| abstract_inverted_index.potential | 292 |
| abstract_inverted_index.regulates | 202 |
| abstract_inverted_index.strongest | 106 |
| abstract_inverted_index.submodule | 13 |
| abstract_inverted_index.validated | 137 |
| abstract_inverted_index.(threonine | 178 |
| abstract_inverted_index.Consistent | 80 |
| abstract_inverted_index.Flo8.Under | 203 |
| abstract_inverted_index.associated | 131 |
| abstract_inverted_index.expression | 100 |
| abstract_inverted_index.formation. | 96, 220 |
| abstract_inverted_index.functional | 64 |
| abstract_inverted_index.importance | 293 |
| abstract_inverted_index.inhibition | 89, 110, 153 |
| abstract_inverted_index.negatively | 201 |
| abstract_inverted_index.phenotype, | 249 |
| abstract_inverted_index.phenotypes | 37 |
| abstract_inverted_index.positively | 166 |
| abstract_inverted_index.potential. | 134 |
| abstract_inverted_index.previously | 136 |
| abstract_inverted_index.substrates | 130 |
| abstract_inverted_index.sufficient | 184 |
| abstract_inverted_index.suggesting | 196 |
| abstract_inverted_index.activities. | 304 |
| abstract_inverted_index.conditions, | 205 |
| abstract_inverted_index.considering | 295 |
| abstract_inverted_index.identified. | 143 |
| abstract_inverted_index.metabolism, | 41 |
| abstract_inverted_index.morphology, | 40 |
| abstract_inverted_index.morphology. | 171 |
| abstract_inverted_index.phenotypes, | 88 |
| abstract_inverted_index.resistance. | 49 |
| abstract_inverted_index.selectively | 73 |
| abstract_inverted_index.underscores | 290 |
| abstract_inverted_index.Furthermore, | 97 |
| abstract_inverted_index.acquisition, | 43 |
| abstract_inverted_index.inactivation | 117 |
| abstract_inverted_index.interactions | 285 |
| abstract_inverted_index.phosphosites | 177 |
| abstract_inverted_index.specifically | 150 |
| abstract_inverted_index.utilization, | 263 |
| abstract_inverted_index.co-regulation | 22 |
| abstract_inverted_index.filamentation | 133 |
| abstract_inverted_index.interactions, | 46 |
| abstract_inverted_index.morphological | 194 |
| abstract_inverted_index.multi-subunit | 16 |
| abstract_inverted_index.transcription | 162, 257, 302 |
| abstract_inverted_index.alkalinization | 234, 248 |
| abstract_inverted_index.hypha-specific | 102 |
| abstract_inverted_index.transcription. | 24 |
| abstract_inverted_index.phosphorylation | 145 |
| abstract_inverted_index.transcriptional | 107, 192 |
| abstract_inverted_index.transcriptomics | 114 |
| abstract_inverted_index.phosphoproteomic | 123 |
| abstract_inverted_index.hyperfilamentous, | 214 |
| cited_by_percentile_year.max | 99 |
| cited_by_percentile_year.min | 89 |
| corresponding_author_ids | https://openalex.org/A5010005294, https://openalex.org/A5006474038, https://openalex.org/A5013463468, https://openalex.org/A5022828946, https://openalex.org/A5041042735, https://openalex.org/A5075295071, https://openalex.org/A5037494503, https://openalex.org/A5080169755, https://openalex.org/A5072787697 |
| countries_distinct_count | 1 |
| institutions_distinct_count | 9 |
| corresponding_institution_ids | https://openalex.org/I107672454, https://openalex.org/I1289422878 |
| sustainable_development_goals[0].id | https://metadata.un.org/sdg/3 |
| sustainable_development_goals[0].score | 0.5400000214576721 |
| sustainable_development_goals[0].display_name | Good health and well-being |
| citation_normalized_percentile.value | 0.82077922 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | False |