PXD027190

PXD027190 is an original dataset announced via ProteomeXchange.

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

Revision	Datetime	Status	ChangeLog Entry
0	2021-07-08 09:10:08	ID requested
⏵ 1	2021-12-30 14:26:24	announced

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]

submitter keyword: Microtubule-targeting agents

vincristine

microtubules

acute lymphoblastic leukemia

palbociclib

phosphoproteomics

c-Jun

c-Jun N-terminal kinase

DNA damage response

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

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PRIDE project URI

• PRIDE
  1. PXD027190
     1. Label: PRIDE project
     2. Name: Phosphoproteomics provides novel insights into the response of primary acute lymphoblastic leukemia cells to microtubule depolymerization in G1 phase of the cell cycle