Integrative phosphoproteome and interactome analysis of the role of Ubash3b in BCR-ABL signaling

Cutler, Jevon; Udainiya, Savita; Madugundu, Anil K.; Renuse, Santosh; Xu, Yaoyu; Jung, Jaehun; Kim, Kwang Pyo; Wu, Xinyan; Pandey, Akhilesh

doi:10.1038/s41375-019-0535-4

Cited by 12 publications

(18 citation statements)

References 15 publications

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“…9d ). It should be noted that the stable interaction of CD2AP with STS1 has also been confirmed recently by the BioID approach in leukemia cells 35 . Furthermore, we validated colocalization of CD2AP with STS1 in EGF-induced membrane ruffles and the leading edges of cells (Fig.…”

Section: Resultsmentioning

confidence: 53%

“…In addition, we also explored the protein complexes associated with four cytosolic proteins, including ILK, RSU1, PINCH, and PARVIN. The stable interactome of STS1 has been reported by us and others recently based on both AP-MS 41 , 42 and the BioID approach 35 . In this study, we systematically extended the exploration of the STS1 interactome in a spatiotemporal manner with minute resolution.…”

Section: Discussionmentioning

confidence: 68%

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Spatiotemporal profiling of cytosolic signaling complexes in living cells by selective proximity proteomics

Yuan

et al. 2021

Nat Commun

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Signaling complexes are often organized in a spatiotemporal manner and on a minute timescale. Proximity labeling based on engineered ascorbate peroxidase APEX2 pioneered in situ capture of spatiotemporal membrane protein complexes in living cells, but its application to cytosolic proteins remains limited due to the high labeling background. Here, we develop proximity labeling probes with increased labeling selectivity. These probes, in combination with label-free quantitative proteomics, allow exploring cytosolic protein assemblies such as phosphotyrosine-mediated protein complexes formed in response to minute-scale EGF stimulation. As proof-of-concept, we systematically profile the spatiotemporal interactome of the EGFR signaling component STS1. For STS1 core complexes, our proximity proteomics approach shows comparable performance to affinity purification-mass spectrometry-based temporal interactome profiling, while also capturing additional—especially endosomally-located—protein complexes. In summary, we provide a generic approach for exploring the interactome of mobile cytosolic proteins in living cells at a temporal resolution of minutes.

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Section: Resultsmentioning

confidence: 53%

Section: Discussionmentioning

confidence: 68%

Spatiotemporal profiling of cytosolic signaling complexes in living cells by selective proximity proteomics

Yuan

et al. 2021

Nat Commun

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“…focusing on proteins as a collective functional group rather than focusing down specifically on one protein in a more reductionist manner [144–146]. Hence, while not focusing in-depth on specific protein-protein interactions, albeit an entirely valid scientific endeavor, here we chose to appreciate molecular signaling at a more collective, gestalt, level [147–149]. Our follow-up manuscript on this topic, addresses in a combinatorial manner both a low-dimensionality ( i.e.…”

Section: Discussionmentioning

confidence: 99%

The RXFP3 receptor is functionally associated with cellular responses to oxidative stress and DNA damage

Gastel

Leysen

Santos‐Otte

et al. 2019

Aging

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DNA damage response (DDR) processes, often caused by oxidative stress, are important in aging and -related disorders. We recently showed that G protein-coupled receptor (GPCR) kinase interacting protein 2 (GIT2) plays a key role in both DNA damage and oxidative stress. Multiple tissue analyses in GIT2KO mice demonstrated that GIT2 expression affects the GPCR relaxin family peptide 3 receptor (RXFP3), and is thus a therapeutically-targetable system. RXFP3 and GIT2 play similar roles in metabolic aging processes. Gaining a detailed understanding of the RXFP3-GIT2 functional relationship could aid the development of novel anti-aging therapies. We determined the connection between RXFP3 and GIT2 by investigating the role of RXFP3 in oxidative stress and DDR. Analyzing the effects of oxidizing (H2O2) and DNA-damaging (camptothecin) stressors on the interacting partners of RXFP3 using Affinity Purification-Mass Spectrometry, we found multiple proteins linked to DDR and cell cycle control. RXFP3 expression increased in response to DNA damage, overexpression, and Relaxin 3-mediated stimulation of RXFP3 reduced phosphorylation of DNA damage marker H2AX, and repair protein BRCA1, moderating DNA damage. Our data suggests an RXFP3-GIT2 system that could regulate cellular degradation after DNA damage, and could be a novel mechanism for mitigating the rate of age-related damage accumulation.

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“…Recent studies confirmed a negative regulatory role of UBASH3b in p210 expressing cells [ 73 ]. UBASH3b knockdown caused hyperphosphorylation of several proteins crucial for leukomegenesis, such as p210 and STAT5, in sites important for their activity [ 74 ]. Lack of UBASH3b also increased p210 interaction with STAT5 and CRK, showing that UBASH3b partially downregulates p210 interactome [ 74 ].…”

Section: Similarities and Differences In Signaling Mediated By P19mentioning

confidence: 99%

Philadelphia Chromosome-Positive Leukemia in the Lymphoid Lineage—Similarities and Differences with the Myeloid Lineage and Specific Vulnerabilities

Komorowski

Fidyt

Patkowska

et al. 2020

IJMS

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Philadelphia chromosome (Ph) results from a translocation between the breakpoint cluster region (BCR) gene on chromosome 9 and ABL proto-oncogene 1 (ABL1) gene on chromosome 22. The fusion gene, BCR-ABL1, is a constitutively active tyrosine kinase which promotes development of leukemia. Depending on the breakpoint site within the BCR gene, different isoforms of BCR-ABL1 exist, with p210 and p190 being the most prevalent. P210 isoform is the hallmark of chronic myeloid leukemia (CML), while p190 isoform is expressed in majority of Ph-positive B cell acute lymphoblastic leukemia (Ph+ B-ALL) cases. The crucial component of treatment protocols of CML and Ph+ B-ALL patients are tyrosine kinase inhibitors (TKIs), drugs which target both BCR-ABL1 isoforms. While TKIs therapy is successful in great majority of CML patients, Ph+ B-ALL often relapses as a drug-resistant disease. Recently, the high-throughput genomic and proteomic analyses revealed significant differences between CML and Ph+ B-ALL. In this review we summarize recent discoveries related to differential signaling pathways mediated by different BCR-ABL1 isoforms, lineage-specific genetic lesions, and metabolic reprogramming. In particular, we emphasize the features distinguishing Ph+ B-ALL from CML and focus on potential therapeutic approaches exploiting those characteristics, which could improve the treatment of Ph+ B-ALL.

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Integrative phosphoproteome and interactome analysis of the role of Ubash3b in BCR-ABL signaling

Cited by 12 publications

References 15 publications

Spatiotemporal profiling of cytosolic signaling complexes in living cells by selective proximity proteomics

Spatiotemporal profiling of cytosolic signaling complexes in living cells by selective proximity proteomics

The RXFP3 receptor is functionally associated with cellular responses to oxidative stress and DNA damage

Philadelphia Chromosome-Positive Leukemia in the Lymphoid Lineage—Similarities and Differences with the Myeloid Lineage and Specific Vulnerabilities

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