PXD037311

PXD037311 is an original dataset announced via ProteomeXchange.

Title	AP-MS of small molecule that selectively destabilizes Cryptochrome 1
Description	Cryptochromes are negative transcriptional regulators of the circadian clock in mammals. It is not clear how reducing the level of endogenous CRY1 in mammals will affect circadian rhythm and the relation of such a decrease with apoptosis. Here, we discovered a molecule (M47) that destabilizes Cryptochrome 1 (CRY1) both in vitro and in vivo. The M47 selectively enhanced the degradation rate of CRY1 by increasing its ubiquitination and resulted in increasing the circadian period length of U2OS Bmal1-dLuc cells. In addition, subcellular fractionation studies from mice liver indicated that M47 increased degradation of the CRY1 in the nucleus. Furthermore, M47-mediated CRY1 reduction enhanced cisplatin-induced apoptosis in Ras-transformed p53 null fibroblast cells. Systemic repetitive administration of M47 increased the median lifespan of p53-/- mice by ~25%. Collectively our data suggest that M47 is a very promising molecule to treat forms of cancer depending on the p53 mutation.
HostingRepository	PRIDE
AnnounceDate	2022-11-07
AnnouncementXML	Submission_2022-11-07_01:23:19.798.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	AliYurtseven
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue; acetylated residue; monohydroxylated residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2022-10-12 08:23:02	ID requested
⏵ 1	2022-11-07 01:23:20	announced

Dataset with its publication pending

submitter keyword: AP-MS,Mouse, Small molecule

HalilKavakli
contact affiliation	Koc University
contact email	hkavakli@ku.edu.tr
lab head
AliYurtseven
contact affiliation	Istanbul
contact email	ayurtseven19@ku.edu.tr
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD037311
     1. Label: PRIDE project
     2. Name: AP-MS of small molecule that selectively destabilizes Cryptochrome 1