PXD008743

PXD008743 is an original dataset announced via ProteomeXchange.

Title	Proteotranscriptomic profiling of potential E6AP targets
Description	Prostate cancer is a common cause of cancer-related death in men. E6AP, an E3 ubiquitin ligase and a transcription cofactor, is elevated in a subset of prostate cancer patients. Genetic manipulations of E6AP in prostate cancer cells expose a role of E6AP in promoting growth and survival of prostate cancer cells in vitro and in vivo. However, the effect of E6AP on prostate cancer cells is broad and it cannot be explained fully by previously identified tumour suppressors, promyelocytic leukemia protein and p27, that are regulated by E6AP. To explore additional players that are regulated downstream of E6AP, we combined a transcriptomic and proteomic approaches. We identified and quantified 16,130 transcripts and 7,209 proteins in castration resistant prostate cancer cell line, DU145. A total of 2,763 transcripts and 308 proteins were considered significantly altered upon knockdown of E6AP. Pathway analyses supported the known phenotypic effect of E6AP knockdown in prostate cancer cells and in parallel exposed novel potential links of E6AP with cancer metabolism, DNA damage repair and immune response. Changes in expression of the top candidates were confirmed using real-time polymerase chain reaction. Of these, clusterin, a stress-induced chaperone protein commonly deregulated in prostate cancer was pursued further. Knockdown of E6AP resulted in increased clusterin transcript and protein levels in vitro and in vivo. Concomitant knockdown of E6AP and clusterin supported the contribution of clusterin to the phenotype induced by E6AP. Overall, results from this study provide insight intothe potential biological pathways controlled by E6AP in prostate cancer cells and identifies clusterin as a novel target of E6AP.
HostingRepository	PRIDE
AnnounceDate	2018-02-27
AnnouncementXML	Submission_2018-02-27_04:44:31.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ralf Schittenhelm
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2018-01-24 01:07:36	ID requested
⏵ 1	2018-02-27 04:44:32	announced

Gulati T, Huang C, Caramia F, Raghu D, Paul PJ, Goode RJA, Keam SP, Williams SG, Haupt S, Kleifeld O, Schittenhelm RB, Gamell C, Haupt Y, Proteotranscriptomic Measurements of E6-Associated Protein (E6AP) Targets in DU145 Prostate Cancer Cells. Mol Cell Proteomics, 17(6):1170-1183(2018) [pubmed]

curator keyword: Biomedical

submitter keyword: E6AP, transcriptomics, SILAC, clusterin, prostate cancer

Ygal Haupt
contact affiliation	The Sir Peter MacCallum Department of Oncology, The University of Melbourne, Victoria, Australia
contact email	Ygal.Haupt@petermac.org
lab head
Ralf Schittenhelm
contact affiliation	Monash University
contact email	ralf.schittenhelm@monash.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD008743
     1. Label: PRIDE project
     2. Name: Proteotranscriptomic profiling of potential E6AP targets