The circadian E3 ligase complex SCFFBXL3+CRY targets TLK2
| Autor: | John R. Yates, Norjin Zolboot, Megan Vaughan, Katja A. Lamia, Valerie Perea, Stephanie Papp Correia, Alanna B. Chan, Anna Kriebs, James J. Moresco, Anne Laure Huber |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Multidisciplinary animal structures biology Kinase Chemistry Circadian clock Ubiquitin-Protein Ligases lcsh:R lcsh:Medicine Cell cycle Ubiquitin ligase Cell biology 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Ubiquitin biology.protein lcsh:Q sense organs Kinase activity lcsh:Science 030217 neurology & neurosurgery Function (biology) |
| Zdroj: | Scientific Reports, Vol 9, Iss 1, Pp 1-9 (2019) |
| ISSN: | 2045-2322 |
| Popis: | We recently demonstrated that the circadian clock component CRY2 is an essential cofactor in the SCFFBXL3-mediated ubiquitination of c-MYC. Because our demonstration that CRY2 recruits phosphorylated substrates to SCFFBXL3 was unexpected, we investigated the scope of this role by searching for additional substrates of FBXL3 that require CRY1 or CRY2 as cofactors. Here, we describe an affinity purification mass spectrometry (APMS) screen through which we identified more than one hundred potential substrates of SCFFBXL3+CRY1/2, including the cell cycle regulated Tousled-like kinase, TLK2. Both CRY1 and CRY2 recruit TLK2 to SCFFBXL3, and TLK2 kinase activity is required for this interaction. Overexpression or genetic deletion of CRY1 and/or CRY2 decreases or enhances TLK2 protein abundance, respectively. These findings reinforce the idea that CRYs function as co-factors for SCFFBXL3, provide a resource of potential substrates, and establish a molecular connection between the circadian and cell cycle oscillators via CRY-modulated turnover of TLK2. |
| Databáze: | OpenAIRE |
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