Role of Mass Spectrometry in Investigating a Novel Protein: The Example of Tumor Differentiation Factor (TDF)

Author(s):  
Izabela Sokolowska ◽  
Armand G. Ngounou Wetie ◽  
Alisa G. Woods ◽  
Madhuri Jayathirtha ◽  
Costel C. Darie
2015 ◽  
Vol 29 (S1) ◽  
Author(s):  
Devika Channaveerappa ◽  
Armand Ngounou Wetie ◽  
Loredana Lupu ◽  
Adrian Robu ◽  
Alina Zamfir ◽  
...  

2011 ◽  
Vol 287 (3) ◽  
pp. 1719-1733 ◽  
Author(s):  
Izabela Sokolowska ◽  
Alisa G. Woods ◽  
Mary Ann Gawinowicz ◽  
Urmi Roy ◽  
Costel C. Darie

FEBS Journal ◽  
2012 ◽  
Vol 279 (14) ◽  
pp. 2579-2594 ◽  
Author(s):  
Izabela Sokolowska ◽  
Alisa G. Woods ◽  
Mary Ann Gawinowicz ◽  
Urmi Roy ◽  
Costel C. Darie

2021 ◽  
pp. 247255522098577
Author(s):  
Andrew X. Zhang ◽  
Katelyn Cassidy ◽  
Göran Dahl ◽  
Kevin Moreau ◽  
Fiona Pachl ◽  
...  

Mass spectrometry-based proteomics profiling is a discovery tool that enables researchers to understand the mechanisms of action of drug candidates. When applied to proteolysis targeting chimeras (PROTACs) such approaches provide unbiased perspectives of the binding, degradation selectivity, and mechanism related to efficacy and safety. Specifically, global profiling experiments can identify direct degradation events and assess downstream pathway modulation that may result from degradation or off-target inhibition. Targeted proteomics approaches can be used to quantify the levels of relevant E3 ligases and the protein of interest in cell lines and tissues of interest, which can inform the line of sight and provide insights on possible safety liabilities early in the project. Furthermore, proteomics approaches can be applied to understand protein turnover and resynthesis rates and inform on target tractability, as well as pharmacokinetics/pharmacodynamics understanding. In this perspective, we survey the literature around the impact of mass spectrometry-based proteomics in the development of PROTACs and present our envisioned proteomics cascade for supporting targeted protein degradation projects.


2012 ◽  
Vol 59 (6) ◽  
pp. 445-450 ◽  
Author(s):  
Urmi Roy ◽  
Izabela Sokolowska ◽  
Alisa G. Woods ◽  
Costel C. Darie

2013 ◽  
Vol 219 (4) ◽  
pp. 1333-1342 ◽  
Author(s):  
Alisa G. Woods ◽  
Izabela Sokolowska ◽  
Katrin Deinhardt ◽  
Cristinel Sandu ◽  
Costel C. Darie

2012 ◽  
Vol 70 (16) ◽  
pp. 2835-2848 ◽  
Author(s):  
Izabela Sokolowska ◽  
Alisa G. Woods ◽  
Mary Ann Gawinowicz ◽  
Urmi Roy ◽  
Costel C. Darie

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Tianlu Jiang ◽  
Yiwen Xia ◽  
Jialun Lv ◽  
Bowen Li ◽  
Ying Li ◽  
...  

Abstract Background A novel type of noncoding RNA, circRNA has been reported to participate in the occurrence and development of diseases through many mechanisms. The MAPK pathway is a common signal transduction pathway involved in cell proliferation, inflammation and apoptosis and plays a particularly important role in cancers. However, the role of circRNAs related to the MAPK pathway in gastric cancer has not been explored. Methods A bioinformatics analysis was performed to profile and identify the circRNAs involved in the MAPK pathway in gastric cancer. The tumor-suppressive role of circMAPK1 was confirmed both in vitro and in vivo. Mass spectrometry, Western blot and immunofluorescence staining assays were used to validate the existence and expression of MAPK1–109aa. The molecular mechanism of circMAPK1 was investigated by mass spectrometry and immunoprecipitation analyses. Results In this study, we identified that circMAPK1 (hsa_circ_0004872) was downregulated in gastric cancer tissues compared with adjacent normal tissues. Importantly, lower circMAPK1 expression predicted poor survival in GC patients. CircMAPK1 inhibited the proliferation and invasion of gastric cancer cells in vitro and in vivo. Next, we found that circMAPK1 encoded a novel protein with 109 amino acids in length. Through a series of functional experiments, we confirmed that circMAPK1 exerted a tumor-suppressing effect via the encoded protein MAPK1–109aa. Mechanistically, the tumor suppressor MAPK1–109aa inhibited the phosphorylation of MAPK1 by competitively binding to MEK1, thereby suppressing the activation of MAPK1 and its downstream factors in MAPK pathway. Conclusions Our study revealed that circMAPK1 inhibits the malignant biological behavior of gastric cancer cells through its encoded protein MAPK1–109aa. More importantly, circMAPK1 is a favorable predictor for gastric cancer patients and may provide a new therapeutic target in the treatment of gastric cancer.


2013 ◽  
Vol 32 (7) ◽  
pp. 512-518 ◽  
Author(s):  
Urmi Roy ◽  
Alisa G. Woods ◽  
Izabela Sokolowska ◽  
Costel C. Darie

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