PXD016417

PXD016417 is an original dataset announced via ProteomeXchange.

Title	The human cholesterogenic enzymes DHCR14 and LBR are differentially regulated transcriptionally and post-translationally
Description	Cholesterol synthesis is a tightly regulated process, both transcriptionally and post-translationally. Transcriptional control of cholesterol synthesis is relatively well understood. However, of the ~20 enzymes in cholesterol biosynthesis, post-translational regulation has only been examined for a small number. Three of the four sterol reductases, DHCR7, DHCR14 and LBR, share evolutionary ties with a high level of sequence homology and predicted structural homology. Despite their homology and that they uniquely share the same 14 reductase activity in cholesterol biosynthesis, little is known about the post-translational regulation of DHCR14 and LBR. Using CHO-7 cells stably expressing epitope tagged DHCR14 or LBR we investigated the post-translational regulation of these enzymes. We found that DHCR14 and LBR undergo differential post translational regulation, with DHCR14 being rapidly turned over, triggered by cholesterol and other sterol intermediates while LBR remained stable. DHCR14 is degraded via the ubiquitin-proteasome system and we identified several DHCR14 and DHCR7 putative interaction partners including the E3 ligase WWP2, which plays a role in the basal and cholesterol-mediated regulation of DHCR14. Interestingly, we found that gene expression across an array of human tissues showed that the C14-SRs gene expression is negatively related; one enzyme or the other tends to be predominately expressed in each tissue. Overall, our findings indicate that while LBR tends to be the constitutively active C14-SR, DHCR14 levels are tuneable, responding to the local cellular demands for cholesterol.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_04:59:18.471.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Gene Hart-Smith
SpeciesList	scientific name: Cricetulus griseus (Chinese hamster) (Cricetulus barabensis griseus); NCBI TaxID: 10029; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos; LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2019-11-25 01:41:09	ID requested
1	2020-01-17 05:59:48	announced
⏵ 2	2024-10-22 04:59:23	announced	2024-10-22: Updated project metadata.

10.1074/jbc.ra119.011323;

Capell-Hattam IM, Sharpe LJ, Qian L, Hart-Smith G, Prabhu AV, Brown AJ, Twin enzymes, divergent control: The cholesterogenic enzymes DHCR14 and LBR are differentially regulated transcriptionally and post-translationally. J Biol Chem, 295(9):2850-2865(2020) [pubmed]

submitter keyword: DHCR14, LBR,cholesterol synthesis enzymes

Andrew J Brown
contact affiliation	School of Biotechnology and Biomolecular Sciences, UNSW
contact email	aj.brown@unsw.edu.au
lab head
Gene Hart-Smith
contact affiliation	Macquarie University
contact email	gene.hart-smith@mq.edu.au
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2020/01/PXD016417

PRIDE project URI

• PRIDE
  1. PXD016417
     1. Label: PRIDE project
     2. Name: The human cholesterogenic enzymes DHCR14 and LBR are differentially regulated transcriptionally and post-translationally