Casein Kinase 1δ-dependent Wee1 Protein Degradation

Penas, Clara; Ramachandran, Vimal; Simanski, Scott; Lee, Choogon; Madoux, Franck; Rahaim, Ronald J.; Chauhan, Ruchi; Barnaby, Omar S.; Schürer, Stephan C.; Hodder, Peter; Steen, Judith A.; Roush, William; Ayad, Nagi G.

doi:10.1074/jbc.m114.547661

Cited by 22 publications

(38 citation statements)

References 30 publications

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“…44 Similarly, our prior studies have developed and characterized a luciferase fusion of the cell cycle kinase Wee1 to identify small molecule inhibitors that specifically affect endogenous Wee1 turnover. 45 In the case of Wee1, the small molecules inhibited kinases we described as novel regulators of Wee1 turnover. 45 Since kinases are known to control degradation of cell cycle proteins, we asked whether we could adapt our prior strategy to identify kinases controlling degradation of p27 Kip1 .…”

Section: Resultsmentioning

confidence: 99%

“…45 In the case of Wee1, the small molecules inhibited kinases we described as novel regulators of Wee1 turnover. 45 Since kinases are known to control degradation of cell cycle proteins, we asked whether we could adapt our prior strategy to identify kinases controlling degradation of p27 Kip1 . To do this, we created a luciferase fusion of p27 Kip1 for use in small molecule screens to identify kinases controlling endogenous p27…”

Section: Resultsmentioning

confidence: 99%

“…[44][45][46][47][48] In the case of cell cycle proteins, the N-terminus of cyclin B1 has been fused to luciferase and utilized in small molecule screens to identify small molecule inhibitors of the ubiquitin ligase APC/C, which controls cyclin B1 turnover. 44 Similarly, our prior studies have developed and characterized a luciferase fusion of the cell cycle kinase Wee1 to identify small molecule inhibitors that specifically affect endogenous Wee1 turnover.…”

Section: Resultsmentioning

confidence: 99%

“…We then showed that CK1d phosphorylates Wee1 on N-terminal residues required for Wee1 turnover. 43 Thus, our prior studies provided a successful workflow for identifying kinases that interact with cell cycle proteins and induce their subsequent degradation. However, these studies were dependent upon in vitro profiling of small molecules to determine their ability to inhibit or activate kinases.…”

Section: Introductionmentioning

confidence: 99%

“…43 Like p27 Kip1 , phospho-Wee1 is targeted for degradation via an SCF ubiquitin ligase. To identify possible kinases mediating Wee1 recognition by the ligase, we generated a Wee1-luciferase fusion protein, which we expressed in cells treated with putative small molecule kinase inhibitors.…”

Section: Introductionmentioning

confidence: 99%

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Screening of cell cycle fusion proteins to identify kinase signaling networks

et al. 2015

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Abbreviations: PMA, Phorbol 12-myristate 13-acetate; S/B, Signal to background ratio; Z 0 , Z factor.Kinase signaling networks are well-established mediators of cell cycle transitions. However, how kinases interact with the ubiquitin proteasome system (UPS) to elicit protein turnover is not fully understood. We sought a means of identifying kinase-substrate interactions to better understand signaling pathways controlling protein degradation. Our prior studies used a luciferase fusion protein to uncover kinase networks controlling protein turnover. In this study, we utilized a similar approach to identify pathways controlling the cell cycle protein p27 Kip1 . We generated a p27 Kip1 -luciferase fusion and expressed it in cells incubated with compounds from a library of pharmacologically active compounds. We then compared the relative effects of the compounds on p27Kip1 -luciferase fusion stabilization. This was combined with in silico kinome profiling to identify potential kinases inhibited by each compound. This approach effectively uncovered known kinases regulating p27Kip1 turnover. Collectively, our studies suggest that this parallel screening approach is robust and can be applied to fully understand kinase-ubiquitin pathway interactions.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Screening of cell cycle fusion proteins to identify kinase signaling networks

et al. 2015

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Smurf1 controls S phase progression and tumorigenesis through Wee1 degradation

Wei

Guo

et al. 2017

FEBS Letters

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Smad ubiquitination regulatory factor 1 (Smurf1) is a HECT-type E3 ubiquitin ligase that regulates several important signaling pathways, including the bone morphogenetic protein pathway and the transforming growth factor-beta (TGF-β) signaling pathway. However, the function of Smurf1 in cell cycle progression remains unclear. Here, we demonstrate that silencing of Smurf1 results in S phase arrest, confirming that Smurf1 is required for S phase progression. Furthermore, we demonstrate that Smurf1-mediated S phase progression is largely dependent on the ubiquitination-dependent degradation of Wee1. This study defines a novel role for Smurf1 in controlling S phase progression by promoting Wee1 degradation.

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Modulation of adenylate cyclase signaling in association with MKK3/6 stabilization under combination of SAC and berberine to reduce HepG2 cell survivability

et al. 2017

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Cancer cells often have faulty apoptotic pathways resulting in sustenance of survivability, tumour metastasis and resistance to anticancer drugs. Alternate strategies are sought to improve therapeutic efficacy and therefore HepG2 cells were treated with S-allyl-cysteine (SAC) and berberine (BER) to analyze their mechanistic impact upon necroptosis along with its interacting relationship to apoptosis. In the present study we observed that SAC and BER exposure reduced NFκβ nuclear translocation through adenylate cyclase-cAMP-protein kinaseA axis and eventually evaded c-FLIP inhibition. Effective RIP1 k63-polyubiquitination and persistent MKK3/MKK6 expression during drug treatment potentiated caspase8 activity via p53-DISC conformation. Resultant tBid associated lysosomal protease mediated AIF truncation induced DNA fragmentation and persuaded effector caspase mediated scramblase activation resulting induction of necroptosis in parallel to apoptotic events. SAC+BER effectively reduced Rb-phosphorylation resulting insignificant nuclear E2F presence led to ending of cell proliferation. Therefore necroptosis augmented the drug response and may be targeted alongside cell proliferation inhibition in formation of efficient therapeutics against liver cancer.

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Casein Kinase 1δ-dependent Wee1 Protein Degradation

Cited by 22 publications

References 30 publications

Screening of cell cycle fusion proteins to identify kinase signaling networks

Screening of cell cycle fusion proteins to identify kinase signaling networks

Smurf1 controls S phase progression and tumorigenesis through Wee1 degradation

Modulation of adenylate cyclase signaling in association with MKK3/6 stabilization under combination of SAC and berberine to reduce HepG2 cell survivability

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