Dataset Information

QUANTITATIVE PHOSPHOPROTEOMIC PROFILING OF PRIMARY RETINOBLASTOMA TUMORS

ABSTRACT: Retinoblastoma is a malignant tumor of the retina which most often occurs in children below 5 years of age with an incident rate of about 1 in 15,000 to 18,000 live births. Retinoblastoma is the first ever cancer that was reported to have a genetic basis. It occurs widely due to inactivating mutations in RB1 gene. Gene expression studies, copy number variation analysis, epigenetic profiling including miRNA and methylation of retinoblastoma has been carried to understand the disease mechanism and key players in the disease. Our group has earlier performed differential proteomics of retinoblastoma to identify proteins of therapeutic importance. However, there are no studies to understand the signalling mechanisms associated with retinoblastoma. Hence, global phosphoproteomics of retinoblastoma was carried out to identify signalling events associated with this cancer. Our study identified stress response proteins to be hyper phosphorylated which included H2AFX and sirtuin 1. In particular, Ser140 of H2AFX also known as gamma-H2AX was found to be hyperphosphorylated in retinoblastoma that indicated activation of DNA damage response pathways. We also observed activation of anti-apoptotic proteins in retinoblastoma compared to control. These observations showed activation of survival pathways and signalling networks activated in tumors.

INSTRUMENT(S): LTQ Orbitrap Elite

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Retina

DISEASE(S): Retinoblastoma

SUBMITTER: Sailaja Elchuri

LAB HEAD: Sailaja Elchuri

PROVIDER: PXD007228 | Pride | 2019-11-11

REPOSITORIES: Pride

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Publications

Phosphoproteomics of Retinoblastoma: A Pilot Study Identifies Aberrant Kinases.

Selvan Lakshmi Dhevi Nagarajha LDN Danda Ravikanth R Madugundu Anil K AK Puttamallesh Vinuth N VN Sathe Gajanan J GJ Krishnan Uma Maheswari UM Khetan Vikas V Rishi Pukhraj P Prasad Thottethodi Subrahmanya Keshava TSK Pandey Akhilesh A Krishnakumar Subramanian S Gowda Harsha H Elchuri Sailaja V SV

Molecules (Basel, Switzerland) 20180615 6

Retinoblastoma is a malignant tumour of the retina which most often occurs in children. Earlier studies on retinoblastoma have concentrated on the identification of key players in the disease and have not provided information on activated/inhibited signalling pathways. The dysregulation of protein phosphorylation in cancer provides clues about the affected signalling cascades in cancer. Phosphoproteomics is an ideal tool for the study of phosphorylation changes in proteins. Hence, global phospho ...[more]

PMID: 29914080

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Project description:The hypothalamus is an anatomically small, but functionally crucial region of the human brain. Normal hypothalamus functioning is central to the regulation of neuroendocrine and neurovegetative systems as well as modulation of chronobiology and behavioral aspects of the human body. Till date the human hypothalamus proteome profile is lacking from literature. In this study, we attempt to delineate the human hypothalamus proteome using high-resolution mass spectrometry approach. We identified a total of 5,349 proteins in the proteomics study. The unassigned spectra from the proteomics study were further used for identifying multiple post translational modification sites as well as for proteogenomics analysis. This resulted in the identification of 616 additional proteins. We observed a higher representation of mitochondrial and synaptic proteins in the proteomics data, as well as enrichment of pathways supporting the hypothalamic involvement in autophagy and adult neurogenesis. Interestingly, the phospholipase D signaling pathway emerged as a junction to the various aspects of hypothalamic functions, and relation to neurodegenerative disorders. Additionally, the investigation for multiple post translational modifications led to the identification of several known and novel post translational modification sites. A total of 13,544 peptides corresponding to 2,542 proteins with modifications of R/K-methylation, S/T/Y-phosphorylation, N/Q-deamidation, R-citrullination, and K-acetylation have been reported in this study. Proteogenomic analysis of hypothalamus resulted in the identification of 291 GSSPs which were further categorised into probable gene correction events. Among these, we confirmed 28 peptides to confer evidence for 10 predicted pseudogenes with coding potential, 4 novel protein-coding (3 novel isoforms, and 1 novel SEP), and 3 protein correction (1 novel exon, 1 alternate frame of translation and 1 N-terminal protein extension) events. We believe that hypothalamic proteome would aid as a platform to decipher the molecular basis for the diverse range of functions performed by this region and provide a baseline for exploring the role of these proteins in neurological health and disorders.

Dataset Information

QUANTITATIVE PHOSPHOPROTEOMIC PROFILING OF PRIMARY RETINOBLASTOMA TUMORS

Publications

Phosphoproteomics of Retinoblastoma: A Pilot Study Identifies Aberrant Kinases.

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