PXD027190 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Phosphoproteomics provides novel insights into the response of primary acute lymphoblastic leukemia cells to microtubule depolymerization in G1 phase of the cell cycle |
Description | Microtubule targeting agents (MTAs) have been used for the treatment of cancer for many decades and are among the most successful chemotherapeutic agents. However, their application and effectiveness is limited because of toxicity and resistance as well as a lack of knowledge of molecular mechanisms downstream of microtubule inhibition. Insight into key pathways that link microtubule disruption to cell death is critical for optimal use of these drugs, for defining biomarkers useful in patient stratification, and for informed design of drug combinations. Although MTAs characteristically induce death in mitosis, microtubule destabilizing agents such as vincristine also induce death directly in G1 phase in primary acute lymphoblastic leukemia (ALL) cells. Because many signaling pathways regulating cell survival and death involve changes in protein expression and phosphorylation, we undertook a comprehensive quantitative proteomic study of G1 phase ALL cells treated with vincristine. The results revealed distinct alterations associated with c-Jun N-terminal kinase signaling, anti-proliferative signaling, the DNA damage response, and cytoskeletal remodeling. Signals specifically associated with cell death were identified by pre-treatment with the CDK4/6 inhibitor palbociclib, which caused G1 arrest and precluded death induction. These results provide insight into signaling mechanisms regulating cellular responses to microtubule inhibition, and provide a foundation for a better understanding of the clinical mechanisms of MTAs and for the design of novel drug combinations. |
HostingRepository | PRIDE |
AnnounceDate | 2021-12-30 |
AnnouncementXML | Submission_2021-12-30_14:26:23.403.xml |
DigitalObjectIdentifier | https://dx.doi.org/10.6019/PXD027190 |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Supported dataset by repository |
PrimarySubmitter | Stephanie Byrum |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | monohydroxylated residue; iodoacetamide derivatized residue |
Instrument | Orbitrap Fusion Lumos |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2021-07-08 09:10:08 | ID requested | |
⏵ 1 | 2021-12-30 14:26:24 | announced | |
Publication List
Delgado M, Washam CL, Urbaniak A, Heflin B, Storey AJ, Lan RS, Mackintosh SG, Tackett AJ, Byrum SD, Chambers TC, Phosphoproteomics Provides Novel Insights into the Response of Primary Acute Lymphoblastic Leukemia Cells to Microtubule Depolymerization in G1 Phase of the Cell Cycle. ACS Omega, 6(38):24949-24959(2021) [pubmed] |
Keyword List
submitter keyword: Microtubule-targeting agents |
vincristine |
microtubules |
acute lymphoblastic leukemia |
palbociclib |
phosphoproteomics |
c-Jun |
c-Jun N-terminal kinase |
DNA damage response |
Contact List
Timothy C. Chambers |
contact affiliation | Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA |
contact email | ChambersTimothyC@uams.edu |
lab head | |
Stephanie Byrum |
contact affiliation | UAMS |
contact email | sbyrum@uams.edu |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD027190
- Label: PRIDE project
- Name: Phosphoproteomics provides novel insights into the response of primary acute lymphoblastic leukemia cells to microtubule depolymerization in G1 phase of the cell cycle