» Articles » PMID: 31816600

Histone Proteomics Reveals Novel Post-translational Modifications in Breast Cancer

Overview
Specialty Geriatrics
Date 2019 Dec 10
PMID 31816600
Citations 7
Authors
Affiliations
Soon will be listed here.
Abstract

Histones and their variants are subjected to several post-translational modifications (PTMs). Histones PTMs play an important role in the regulation of gene expression and are critical for the development and progression of many types of cancer, including breast cancer. In this study, we used two-dimensional TAU/SDS electrophoresis, coupled with mass spectrometry for a comprehensive profiling of histone PTMs in breast cancer cell lines.Proteomic approach allowed us to identify 85 histone PTMs, seventeen of which are not reported in the UniProt database. Western blot analysis was performed to confirm a peculiar pattern of PTMs in the sporadic and hereditary breast cancer cell lines compared to normal cells. Overlapping mass spectrometry data with western blotting results, we identified, for the first time to our knowledge, a tyrosine phosphorylation on histone H1, which is significantly higher in breast cancer cells. Additionally, by inhibiting specific signaling paths, such as PI3K, PPARγ and FAK pathways, we established a correlation between their regulation and the presence of new histone PTMs. Our results may provide new insight on the possible implication of these modifications in breast cancer and may offer new perspectives for future clinical applications.

Citing Articles

Transcriptomic era of cancers in females: new epigenetic perspectives and therapeutic prospects.

Zhu R, Ni J, Ren J, Li D, Xu J, Yu X Front Oncol. 2024; 14:1464125.

PMID: 39605897 PMC: 11598703. DOI: 10.3389/fonc.2024.1464125.


Post-Translation Modifications and Mutations of Human Linker Histone Subtypes: Their Manifestation in Disease.

Kumar A, Maurya P, Hayes J Int J Mol Sci. 2023; 24(2).

PMID: 36674981 PMC: 9860689. DOI: 10.3390/ijms24021463.


Molecular and Cellular Functions of the Linker Histone H1.2.

Lai S, Jia J, Cao X, Zhou P, Gao S Front Cell Dev Biol. 2022; 9:773195.

PMID: 35087830 PMC: 8786799. DOI: 10.3389/fcell.2021.773195.


Changes in Protein Structural Motifs upon Post-Translational Modification in Kidney Cancer.

Tikhonov D, Kulikova L, Rudnev V, Kopylov A, Taldaev A, Stepanov A Diagnostics (Basel). 2021; 11(10).

PMID: 34679534 PMC: 8534394. DOI: 10.3390/diagnostics11101836.


Citrullination and PAD Enzyme Biology in Type 1 Diabetes - Regulators of Inflammation, Autoimmunity, and Pathology.

Yang M, Sodre F, Mamula M, Overbergh L Front Immunol. 2021; 12:678953.

PMID: 34140951 PMC: 8204103. DOI: 10.3389/fimmu.2021.678953.


References
1.
Tachibana M, Sugimoto K, Nozaki M, Ueda J, Ohta T, Ohki M . G9a histone methyltransferase plays a dominant role in euchromatic histone H3 lysine 9 methylation and is essential for early embryogenesis. Genes Dev. 2002; 16(14):1779-91. PMC: 186403. DOI: 10.1101/gad.989402. View

2.
Fraga M, Ballestar E, Villar-Garea A, Boix-Chornet M, Espada J, Schotta G . Loss of acetylation at Lys16 and trimethylation at Lys20 of histone H4 is a common hallmark of human cancer. Nat Genet. 2005; 37(4):391-400. DOI: 10.1038/ng1531. View

3.
Bradford M . A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976; 72:248-54. DOI: 10.1016/0003-2697(76)90527-3. View

4.
Gaspari M, Cuda G . Nano LC-MS/MS: a robust setup for proteomic analysis. Methods Mol Biol. 2011; 790:115-26. DOI: 10.1007/978-1-61779-319-6_9. View

5.
Concolino A, Olivo E, Tamme L, Fiumara C, De Angelis M, Quaresima B . Proteomics Analysis to Assess the Role of Mitochondria in BRCA1-Mediated Breast Tumorigenesis. Proteomes. 2018; 6(2). PMC: 6027205. DOI: 10.3390/proteomes6020016. View