The circadian E3 ligase complex SCFFBXL3+CRY targets TLK2

Stephanie Papp Correia, Alanna B. Chan, Megan Vaughan, Norjin Zolboot, Valerie Perea, Anne Laure Huber, Anna Kriebs, James J. Moresco, John R. Yates, Katja A. Lamia

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Article number198
JournalScientific reports
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2019
Externally publishedYes

Fingerprint

Ubiquitin-Protein Ligases
Cell Cycle
Phosphotransferases
Circadian Clocks
Ubiquitination
Mass Spectrometry
Proteins

ASJC Scopus subject areas

  • General

Cite this

Correia, S. P., Chan, A. B., Vaughan, M., Zolboot, N., Perea, V., Huber, A. L., ... Lamia, K. A. (2019). The circadian E3 ligase complex SCFFBXL3+CRY targets TLK2. Scientific reports, 9(1), [198]. https://doi.org/10.1038/s41598-018-36618-3

The circadian E3 ligase complex SCFFBXL3+CRY targets TLK2. / Correia, Stephanie Papp; Chan, Alanna B.; Vaughan, Megan; Zolboot, Norjin; Perea, Valerie; Huber, Anne Laure; Kriebs, Anna; Moresco, James J.; Yates, John R.; Lamia, Katja A.

In: Scientific reports, Vol. 9, No. 1, 198, 01.12.2019.

Research output: Contribution to journalArticle

Correia, SP, Chan, AB, Vaughan, M, Zolboot, N, Perea, V, Huber, AL, Kriebs, A, Moresco, JJ, Yates, JR & Lamia, KA 2019, 'The circadian E3 ligase complex SCFFBXL3+CRY targets TLK2', Scientific reports, vol. 9, no. 1, 198. https://doi.org/10.1038/s41598-018-36618-3
Correia SP, Chan AB, Vaughan M, Zolboot N, Perea V, Huber AL et al. The circadian E3 ligase complex SCFFBXL3+CRY targets TLK2. Scientific reports. 2019 Dec 1;9(1). 198. https://doi.org/10.1038/s41598-018-36618-3
Correia, Stephanie Papp ; Chan, Alanna B. ; Vaughan, Megan ; Zolboot, Norjin ; Perea, Valerie ; Huber, Anne Laure ; Kriebs, Anna ; Moresco, James J. ; Yates, John R. ; Lamia, Katja A. / The circadian E3 ligase complex SCFFBXL3+CRY targets TLK2. In: Scientific reports. 2019 ; Vol. 9, No. 1.
@article{051088de080f4af281ef9f6e52a01c35,
title = "The circadian E3 ligase complex SCFFBXL3+CRY targets TLK2",
abstract = "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.",
author = "Correia, {Stephanie Papp} and Chan, {Alanna B.} and Megan Vaughan and Norjin Zolboot and Valerie Perea and Huber, {Anne Laure} and Anna Kriebs and Moresco, {James J.} and Yates, {John R.} and Lamia, {Katja A.}",
year = "2019",
month = "12",
day = "1",
doi = "10.1038/s41598-018-36618-3",
language = "English (US)",
volume = "9",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
number = "1",

}

TY - JOUR

T1 - The circadian E3 ligase complex SCFFBXL3+CRY targets TLK2

AU - Correia, Stephanie Papp

AU - Chan, Alanna B.

AU - Vaughan, Megan

AU - Zolboot, Norjin

AU - Perea, Valerie

AU - Huber, Anne Laure

AU - Kriebs, Anna

AU - Moresco, James J.

AU - Yates, John R.

AU - Lamia, Katja A.

PY - 2019/12/1

Y1 - 2019/12/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85060172653&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85060172653&partnerID=8YFLogxK

U2 - 10.1038/s41598-018-36618-3

DO - 10.1038/s41598-018-36618-3

M3 - Article

C2 - 30655559

AN - SCOPUS:85060172653

VL - 9

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

IS - 1

M1 - 198

ER -