Phosphorylation of GAPVD1 Is Regulated by the PER Complex and Linked to GAPVD1 Degradation Article Swipe
Hussam Ibrahim
,
Philipp Reus
,
Anna Katharina Mundorf
,
Anna-Lena Grothoff
,
Valerie Rudenko
,
Christina Buschhaus
,
Anja Stefanski
,
Niklas Berleth
,
Björn Stork
,
Kai Stühler
,
Faiza Kalfalah
,
Hans Reinke
·
YOU?
·
· 2021
· Open Access
·
· DOI: https://doi.org/10.3390/ijms22073787
YOU?
·
· 2021
· Open Access
·
· DOI: https://doi.org/10.3390/ijms22073787
Repressor protein period (PER) complexes play a central role in the molecular oscillator mechanism of the mammalian circadian clock. While the main role of nuclear PER complexes is transcriptional repression, much less is known about the functions of cytoplasmic PER complexes. We found with a biochemical screen for PER2-interacting proteins that the small GTPase regulator GTPase-activating protein and VPS9 domain-containing protein 1 (GAPVD1), which has been identified previously as a component of cytoplasmic PER complexes in mice, is also a bona fide component of human PER complexes. We show that in situ GAPVD1 is closely associated with casein kinase 1 delta (CSNK1D), a kinase that regulates PER2 levels through a phosphoswitch mechanism, and that CSNK1D regulates the phosphorylation of GAPVD1. Moreover, phosphorylation determines the kinetics of GAPVD1 degradation and is controlled by PER2 and a C-terminal autoinhibitory domain in CSNK1D, indicating that the regulation of GAPVD1 phosphorylation is a novel function of cytoplasmic PER complexes and might be part of the oscillator mechanism or an output function of the circadian clock.
Related Topics
Concepts
Phosphorylation
Circadian clock
Casein kinase 1
Cell biology
PER2
Biology
Repressor
GTPase
Nuclear transport
Cytoplasm
Protein kinase A
Chemistry
Biochemistry
CLOCK
Gene
Cell nucleus
Transcription factor
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.3390/ijms22073787
- https://www.mdpi.com/1422-0067/22/7/3787/pdf?version=1617940810
- OA Status
- gold
- Cited By
- 7
- References
- 52
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W3147148500
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W3147148500Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.3390/ijms22073787Digital Object Identifier
- Title
-
Phosphorylation of GAPVD1 Is Regulated by the PER Complex and Linked to GAPVD1 DegradationWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2021Year of publication
- Publication date
-
2021-04-06Full publication date if available
- Authors
-
Hussam Ibrahim, Philipp Reus, Anna Katharina Mundorf, Anna-Lena Grothoff, Valerie Rudenko, Christina Buschhaus, Anja Stefanski, Niklas Berleth, Björn Stork, Kai Stühler, Faiza Kalfalah, Hans ReinkeList of authors in order
- Landing page
-
https://doi.org/10.3390/ijms22073787Publisher landing page
- PDF URL
-
https://www.mdpi.com/1422-0067/22/7/3787/pdf?version=1617940810Direct link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
-
https://www.mdpi.com/1422-0067/22/7/3787/pdf?version=1617940810Direct OA link when available
- Concepts
-
Phosphorylation, Circadian clock, Casein kinase 1, Cell biology, PER2, Biology, Repressor, GTPase, Nuclear transport, Cytoplasm, Protein kinase A, Chemistry, Biochemistry, CLOCK, Gene, Cell nucleus, Transcription factorTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
7Total citation count in OpenAlex
- Citations by year (recent)
-
2025: 2, 2024: 2, 2023: 2, 2013: 1Per-year citation counts (last 5 years)
- References (count)
-
52Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.(PER) | 3 |
| abstract_inverted_index.While | 19 |
| abstract_inverted_index.about | 34 |
| abstract_inverted_index.delta | 100 |
| abstract_inverted_index.found | 42 |
| abstract_inverted_index.human | 84 |
| abstract_inverted_index.known | 33 |
| abstract_inverted_index.mice, | 76 |
| abstract_inverted_index.might | 156 |
| abstract_inverted_index.novel | 149 |
| abstract_inverted_index.small | 52 |
| abstract_inverted_index.which | 63 |
| abstract_inverted_index.CSNK1D | 114 |
| abstract_inverted_index.GAPVD1 | 92, 126, 145 |
| abstract_inverted_index.GTPase | 53 |
| abstract_inverted_index.casein | 97 |
| abstract_inverted_index.clock. | 18, 170 |
| abstract_inverted_index.domain | 137 |
| abstract_inverted_index.kinase | 98, 103 |
| abstract_inverted_index.levels | 107 |
| abstract_inverted_index.output | 165 |
| abstract_inverted_index.period | 2 |
| abstract_inverted_index.screen | 46 |
| abstract_inverted_index.CSNK1D, | 139 |
| abstract_inverted_index.GAPVD1. | 119 |
| abstract_inverted_index.central | 7 |
| abstract_inverted_index.closely | 94 |
| abstract_inverted_index.nuclear | 24 |
| abstract_inverted_index.protein | 1, 56, 60 |
| abstract_inverted_index.through | 108 |
| abstract_inverted_index.function | 150, 166 |
| abstract_inverted_index.kinetics | 124 |
| abstract_inverted_index.proteins | 49 |
| abstract_inverted_index.(CSNK1D), | 101 |
| abstract_inverted_index.(GAPVD1), | 62 |
| abstract_inverted_index.Moreover, | 120 |
| abstract_inverted_index.Repressor | 0 |
| abstract_inverted_index.circadian | 17, 169 |
| abstract_inverted_index.complexes | 4, 26, 74, 154 |
| abstract_inverted_index.component | 70, 82 |
| abstract_inverted_index.functions | 36 |
| abstract_inverted_index.mammalian | 16 |
| abstract_inverted_index.mechanism | 13, 162 |
| abstract_inverted_index.molecular | 11 |
| abstract_inverted_index.regulates | 105, 115 |
| abstract_inverted_index.regulator | 54 |
| abstract_inverted_index.C-terminal | 135 |
| abstract_inverted_index.associated | 95 |
| abstract_inverted_index.complexes. | 40, 86 |
| abstract_inverted_index.controlled | 130 |
| abstract_inverted_index.determines | 122 |
| abstract_inverted_index.identified | 66 |
| abstract_inverted_index.indicating | 140 |
| abstract_inverted_index.mechanism, | 111 |
| abstract_inverted_index.oscillator | 12, 161 |
| abstract_inverted_index.previously | 67 |
| abstract_inverted_index.regulation | 143 |
| abstract_inverted_index.biochemical | 45 |
| abstract_inverted_index.cytoplasmic | 38, 72, 152 |
| abstract_inverted_index.degradation | 127 |
| abstract_inverted_index.repression, | 29 |
| abstract_inverted_index.phosphoswitch | 110 |
| abstract_inverted_index.autoinhibitory | 136 |
| abstract_inverted_index.phosphorylation | 117, 121, 146 |
| abstract_inverted_index.transcriptional | 28 |
| abstract_inverted_index.PER2-interacting | 48 |
| abstract_inverted_index.GTPase-activating | 55 |
| abstract_inverted_index.domain-containing | 59 |
| cited_by_percentile_year.max | 97 |
| cited_by_percentile_year.min | 89 |
| corresponding_author_ids | https://openalex.org/A5039674144 |
| countries_distinct_count | 1 |
| institutions_distinct_count | 12 |
| corresponding_institution_ids | https://openalex.org/I44260953 |
| citation_normalized_percentile.value | 0.54021401 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | False |