HTRA1-Dependent Cell Cycle Proteomics.
Jasmin SchillingerKatharina SeverinFarnusch KaschaniMarkus KaiserMichael EhrmannPublished in: Journal of proteome research (2018)
The HTRA1 gene encoding an evolutionary conserved protein quality-control factor can be epigenetically silenced or inactivated by mutation under pathologic conditions such as cancer. Recent evidence suggests that the loss of HTRA1 function causes multiple phenotypes, including the acceleration of cell growth, delayed onset of senescence, centrosome amplification, and polyploidy, suggesting an implication in the regulation of the cell cycle. To address this model, we performed a large-scale proteomics study to correlate the abundance of proteins and HTRA1 levels in various cell cycle phases using label-free-quantification mass spectrometry. These data indicate that the levels of 4723 proteins fluctuated in a cell-cycle-dependent manner, 2872 in a HTRA1-dependent manner, and 1530 in a cell-cycle- and HTRA1-dependent manner. The large number of proteins affected by the modulation of HTRA1 levels supports its general role in protein homeostasis. Moreover, the detected changes in protein abundance, in combination with pull-down data, implicate HTRA1 in various cell cycle events such as DNA replication, chromosome segregation, and cell-cycle-dependent apoptosis. These results highlight the wide implications of HTRA1 in cellular physiology.
Keyphrases
- cell cycle
- cell proliferation
- label free
- mass spectrometry
- quality control
- genome wide
- oxidative stress
- protein protein
- cell death
- dna methylation
- electronic health record
- dna damage
- squamous cell carcinoma
- liquid chromatography
- antibiotic resistance genes
- papillary thyroid
- amino acid
- endoplasmic reticulum stress
- young adults
- lymph node
- microbial community
- wastewater treatment
- locally advanced
- long noncoding rna
- gas chromatography
- cell cycle arrest
- squamous cell