USP2-Related Cellular Signaling and Consequent Pathophysiological Outcomes
Ubiquitin specific protease (USP) 2 is a multifunctional deubiquitinating enzyme. USP2 modulates cell cycle progression, and therefore carcinogenesis, via the deubiquitination of cyclins and Aurora-A. Other tumorigenic molecules, including epidermal growth factor and fatty acid synthase, are also ta...
| Main Authors: | , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-01-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/22/3/1209 |
| _version_ | 1797407141356634112 |
|---|---|
| author | Hiroshi Kitamura Mayuko Hashimoto |
| author_facet | Hiroshi Kitamura Mayuko Hashimoto |
| author_sort | Hiroshi Kitamura |
| collection | DOAJ |
| description | Ubiquitin specific protease (USP) 2 is a multifunctional deubiquitinating enzyme. USP2 modulates cell cycle progression, and therefore carcinogenesis, via the deubiquitination of cyclins and Aurora-A. Other tumorigenic molecules, including epidermal growth factor and fatty acid synthase, are also targets for USP2. USP2 additionally prevents p53 signaling. On the other hand, USP2 functions as a key component of the CLOCK/BMAL1 complex and participates in rhythmic gene expression in the suprachiasmatic nucleus and liver. USP2 variants influence energy metabolism by controlling hepatic gluconeogenesis, hepatic cholesterol uptake, adipose tissue inflammation, and subsequent systemic insulin sensitivity. USP2 also has the potential to promote surface expression of ion channels in renal and intestinal epithelial cells. In addition to modifying the production of cytokines in immune cells, USP2 also modulates the signaling molecules that are involved in cytokine signaling in the target cells. <i>Usp2</i> knockout mice exhibit changes in locomotion and male fertility, which suggest roles for USP2 in the central nervous system and male genital tract, respectively. In this review, we summarize the cellular events with USP2 contributions and list the signaling molecules that are upstream or downstream of USP2. Additionally, we describe phenotypic differences found in the in vitro and in vivo experimental models. |
| first_indexed | 2024-03-09T03:36:59Z |
| format | Article |
| id | doaj.art-f01ed2d43fe845ef91269b6f05408d2f |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T03:36:59Z |
| publishDate | 2021-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-f01ed2d43fe845ef91269b6f05408d2f2023-12-03T14:47:06ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-01-01223120910.3390/ijms22031209USP2-Related Cellular Signaling and Consequent Pathophysiological OutcomesHiroshi Kitamura0Mayuko Hashimoto1Laboratory of Veterinary Physiology, School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, Hokkaido 069-8501, JapanLaboratory of Veterinary Physiology, School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, Hokkaido 069-8501, JapanUbiquitin specific protease (USP) 2 is a multifunctional deubiquitinating enzyme. USP2 modulates cell cycle progression, and therefore carcinogenesis, via the deubiquitination of cyclins and Aurora-A. Other tumorigenic molecules, including epidermal growth factor and fatty acid synthase, are also targets for USP2. USP2 additionally prevents p53 signaling. On the other hand, USP2 functions as a key component of the CLOCK/BMAL1 complex and participates in rhythmic gene expression in the suprachiasmatic nucleus and liver. USP2 variants influence energy metabolism by controlling hepatic gluconeogenesis, hepatic cholesterol uptake, adipose tissue inflammation, and subsequent systemic insulin sensitivity. USP2 also has the potential to promote surface expression of ion channels in renal and intestinal epithelial cells. In addition to modifying the production of cytokines in immune cells, USP2 also modulates the signaling molecules that are involved in cytokine signaling in the target cells. <i>Usp2</i> knockout mice exhibit changes in locomotion and male fertility, which suggest roles for USP2 in the central nervous system and male genital tract, respectively. In this review, we summarize the cellular events with USP2 contributions and list the signaling molecules that are upstream or downstream of USP2. Additionally, we describe phenotypic differences found in the in vitro and in vivo experimental models.https://www.mdpi.com/1422-0067/22/3/1209ubiquitin-specific proteasetumorigenesiscell cycleinflammationcircadian clockmetabolic disorder |
| spellingShingle | Hiroshi Kitamura Mayuko Hashimoto USP2-Related Cellular Signaling and Consequent Pathophysiological Outcomes International Journal of Molecular Sciences ubiquitin-specific protease tumorigenesis cell cycle inflammation circadian clock metabolic disorder |
| title | USP2-Related Cellular Signaling and Consequent Pathophysiological Outcomes |
| title_full | USP2-Related Cellular Signaling and Consequent Pathophysiological Outcomes |
| title_fullStr | USP2-Related Cellular Signaling and Consequent Pathophysiological Outcomes |
| title_full_unstemmed | USP2-Related Cellular Signaling and Consequent Pathophysiological Outcomes |
| title_short | USP2-Related Cellular Signaling and Consequent Pathophysiological Outcomes |
| title_sort | usp2 related cellular signaling and consequent pathophysiological outcomes |
| topic | ubiquitin-specific protease tumorigenesis cell cycle inflammation circadian clock metabolic disorder |
| url | https://www.mdpi.com/1422-0067/22/3/1209 |
| work_keys_str_mv | AT hiroshikitamura usp2relatedcellularsignalingandconsequentpathophysiologicaloutcomes AT mayukohashimoto usp2relatedcellularsignalingandconsequentpathophysiologicaloutcomes |