Dataset Information

Proteomic Analysis of the Response to Cell Cycle Arrests in Human Myeloid Leukemia Cells

ABSTRACT: Previously (Ly et al. 2014), we analyzed protein abundance changes across a â€˜minimally perturbedâ€™ cell cycle in human cells (NB4), using centrifugal elutriation to differentially enrich distinct cell cycle phases. Here, we compare data from elutriated cells with NB4 cells arrested at comparable phases using serum starvation, hydroxyurea, or RO-3306. While elutriated and arrested cells have similar patterns of DNA content and cyclin expression, a large fraction of the proteome changes detected in arrested cells are found to reflect arrest-specific responses (i.e., starvation, DNA damage, CDK1 inhibition), rather than physiological cell cycle regulation. For example, we show most cells arrested in G2 by CDK1 inhibition express abnormally high levels of replication and origin licensing factors, and are likely poised for genome re-replication. The protein data are available in the Encyclopedia of Proteome Dynamics (http://www.peptracker.com/epd/), an online, searchable resource.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Leukocyte

DISEASE(S): Acute Leukemia

SUBMITTER: Vackar Afzal

LAB HEAD: Angus Lamond

PROVIDER: PXD001610 | Pride | 2015-07-23

REPOSITORIES: Pride

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Publications

Proteomic analysis of the response to cell cycle arrests in human myeloid leukemia cells.

Ly Tony T Endo Aki A Lamond Angus I AI

eLife 20150102

Previously, we analyzed protein abundance changes across a 'minimally perturbed' cell cycle by using centrifugal elutriation to differentially enrich distinct cell cycle phases in human NB4 cells (Ly et al., 2014). In this study, we compare data from elutriated cells with NB4 cells arrested at comparable phases using serum starvation, hydroxyurea, or RO-3306. While elutriated and arrested cells have similar patterns of DNA content and cyclin expression, a large fraction of the proteome changes d ...[more]

PMID: 25555159

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Project description:WNT signaling is critical in most aspects of skeletal development and homeostasis, and antagonists of WNT signaling are emergning as key regulatory proteins with great promise as therapeutic agents for bone disorders. Until recently Sost and its paralog Sostdc1 have been described as growth factors with highly restricted expression in the adult where Sost was assumed 'osteocyte-' and Sostdc1 'kidney-' specific. Here we show that these two proteins emerged throgh ancestral genome duplication and their expression patterns have diverged to span complimentary domains in most organ systems including musculoskeletal, cardiovascular, nervous, digestive, reproductive and respiratory. In the developing limb, Sost and Sostdc1 display dynamic expression patterns with Sost being restricted to the distal ectoderm and Sostdc1 to the proximal ectoderm and the mesenchyme. While Sostdc1-/- mice lack any obvious limb and skeletal defects, Sost-/- mice recapitulate the hand defects described for sclerosteosis patients. However, elevated WNT signaling in Sost-/-; Sostdc1-/- mice causes misregulation of SHH signaling, ectopic activation of Sox9 in the digit 1 field and ultimately preaxial polydactyly. In addition, we show that the syndactyly documented in Sclerosteosis is present in both Sost-/- and Sost-/-; Sostdc1-/- mice, and is driven by misregulation of Fgf8 in the AER, a region lacking Sost and Sostdc1 expression. This study highlights the complexity of WNT signaling in skeletal biology and disease and emphasizes how redundant mechanisms and non-cell autonomous effects can synergize to unveil new intricate phenotypes caused by elevated WNT signaling. Five arrays were analyzed, consisting of two total embryonic fore-limb RNA (experimental) and three total embryonic forelimb RNA (reference) samples at E11.5 DPC mouse (C57Bl6 strain). Embryos were not pooled to generate samples. Each time point has 3 to 5 biological replicates for limb bud samples, duplicates for whole embryos. Comparisons were made between limb bud samples and whole embryo at the same stage, fore-limb samples of different stages, hind-limb samples of different stages, and fore-limb samples compared to hind-limb samples at the same or the next stage.

Dataset Information

Proteomic Analysis of the Response to Cell Cycle Arrests in Human Myeloid Leukemia Cells

Publications

Proteomic analysis of the response to cell cycle arrests in human myeloid leukemia cells.

Similar Datasets

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