PXD005037

PXD005037 is an original dataset announced via ProteomeXchange.

Dataset Summary

Title	Progeroid Syndrome Patients with ZMPSTE24 Deficiency Could Benefit When Treated with Rapamycin and Dimethylsulfoxide
Description	Patients with progeroid syndromes like mandibuloacral dysplasia, type B (MADB) and restrictive dermopathy (RD), harbor mutations in zinc metalloproteinase (ZMPSTE24), an enzyme essential for post-translational proteolysis of prelamin A to form mature lamin A. Dermal fibroblasts from these patients show increased nuclear dysmorphology and reduced proliferation, however, efficacy of various pharmacological agents in reversing these cellular phenotypes remains unknown. In this study, fibroblasts from MADB patients exhibited marked nuclear abnormalities and reduced proliferation which improved upon treatment with rapamycin and dimethylsulfoxide but not with other agents including farnesyl transferase inhibitors. Surprisingly, fibroblasts from an RD patient with homozygous null mutation in ZMPSTE24, resulting in exclusive accumulation of prelamin A with no lamin A on immunoblotting of cellular lysate, exhibited few nuclear abnormalities and near normal cellular proliferation. An unbiased proteomic analysis of the cellular lysate from RD fibroblasts revealed lack of processing of vimentin, a cytoskeletal protein. Interestingly, the assembly of the vimentin microfibrils in MADB fibroblasts improved with rapamycin and dimethylsulfoxide. We conclude that rapamycin and dimethylsulfoxide are beneficial for improving nuclear morphology and cell proliferation of MADB fibroblasts. Data from RD fibroblasts suggest that prelamin A accumulation by itself may not be detrimental.
HostingRepository	MassIVE
AnnounceDate	2016-11-01
AnnouncementXML	Submission_2016-11-01_11:46:07.xml
DigitalObjectIdentifier
ReviewLevel	Non peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Andrew Lemoff
SpeciesList	scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	LTQ Orbitrap Elite

Dataset History

Revision	Datetime	Status	ChangeLog Entry
0	2016-09-26 13:54:45	ID requested
⏵ 1	2016-11-01 11:46:07	announced

Publication List

Dataset with its publication pending

Dataset with its publication pending

Keyword List

submitter keyword: Zmpste24, mandibuloacral dysplasia, DMSO, restrictive dermopathy, rapamycin, vimentin, proteomics, progeroid syndrome

submitter keyword: Zmpste24, mandibuloacral dysplasia, DMSO, restrictive dermopathy, rapamycin, vimentin, proteomics, progeroid syndrome

Contact List

Anil Agarwal
lab head
Andrew Lemoff
contact affiliation	UT-Southwestern Medical Center
contact email	andrew.lemoff@utsw.edu
dataset submitter

Full Dataset Link List

MassIVE dataset URI
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MassIVE dataset URI

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://massive.ucsd.edu/MSV000080191