PXD004440

PXD004440 is an original dataset announced via ProteomeXchange.

Title	Dynarrestin, a novel inhibitor of cytoplasmic dyneins 1 and 2
Description	Aberrant hedgehog (Hh) signaling contributes to the pathogenesis of multiple cancers. Currently available inhibitors target Smoothened, which can acquire mutations causing drug resistance. Thus, compounds that inhibit Hh signaling downstream of Smoothened are urgently needed. We identified dynarrestin, a novel inhibitor of cytoplasmic dyneins 1 and 2 by using achemical proteomics approach. Dynarrestin acts reversibly to inhibit cytoplasmic dynein 1-dependent microtubule binding and motility in vitro without affecting ATP hydrolysis. It rapidly and reversibly inhibits endosome movement in living cells and perturbs mitosis by inducing spindle misorientation and a pseudoprometaphase delay. Dynarrestin reversibly inhibits intraflagellar transport (IFT) of the cargo IFT88 and flux of Smoothened within cilia without interfering with ciliogenesis as well as suppresses Hh-dependent proliferation of neuronal precursors and tumor cells. As such, dynarrestin is a valuable new tool for probing cytoplasmic dynein-dependent cellular processes and a promising lead compound for medicinal chemistry programs aimed at development of anti-cancer drugs.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_04:30:58.931.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Hannes Drexler
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2016-06-24 04:33:53	ID requested
1	2018-08-08 08:25:45	announced
⏵ 2	2024-10-22 04:31:07	announced	2024-10-22: Updated project metadata.

10.1016/j.chembiol.2017.12.014;

H, ö, ing S, Yeh TY, Baumann M, Martinez NE, Habenberger P, Kremer L, Drexler HCA, K, ü, chler P, Reinhardt P, Choidas A, Zischinsky ML, Zischinsky G, Nandini S, Ledray AP, Ketcham SA, Reinhardt L, Abo-Rady M, Glatza M, King SJ, Nussbaumer P, Ziegler S, Klebl B, Schroer TA, Sch, ö, ler HR, Waldmann H, Sterneckert J, Dynarrestin, a Novel Inhibitor of Cytoplasmic Dynein. Cell Chem Biol, 25(4):357-369.e6(2018) [pubmed]

curator keyword: Biological, Biomedical

submitter keyword: hedgehog signalling, small molecule inhibitor,Dynein, dynarrestin

Hannes C. A. Drexler
contact affiliation	Dr. Hannes C.A. Drexler Bioanalytical Mass Spectrometry Max Planck Institute for Molecular Biomedicine Röntgenstr. 20 48149 Münster P:+49-251-70365550 P:+49-251-70365521 F:+49-251-70365299
contact email	hannes.drexler@mpi-muenster.mpg.de
lab head
Hannes Drexler
contact affiliation	Bioanalytical Mass Spectrometry, Max Planck Insitute for Molecular Biomedicine, Roentgenstr. 20, 48149 Münster, Germany
contact email	hannes.drexler@mpi-muenster.mpg.de
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/2018/08/PXD004440

PRIDE project URI

• PRIDE
  1. PXD004440
     1. Label: PRIDE project
     2. Name: Dynarrestin, a novel inhibitor of cytoplasmic dyneins 1 and 2