PXD025123-1

PXD025123 is an original dataset announced via ProteomeXchange.

Title	Dual roles of HSP70 chaperone HSPA1 in quality control of nascent and newly synthesized proteins
Description	Exposure to heat stress triggers a well-defined acute response marked by HSF1-dependent transcriptional upregulation of heat shock proteins. Cells allowed to recover acquire thermotolerance, but this adaptation is poorly understood. By quantitative proteomics, we discovered selective upregulation of HSP70-family chaperone HSPA1 and its co-factors, HSPH1 and DNAJB1, in MCF7 breast cancer cells acquiring thermotolerance. HSPA1 was found to have dual function during heat stress response: (i) during acute stress, it promotes the recruitment of the 26S proteasome to translating ribosomes, thus poising cells for rapid protein degradation and resumption of protein synthesis upon recovery; (ii) during thermotolerance, HSPA1 together with HSPH1 maintains ubiquitylated nascent/newly synthesized proteins in a soluble state required for their efficient proteasomal clearance. Consistently, deletion of HSPH1 impedes thermotolerance and esophageal tumor growth in mice, thus providing a potential explanation for the poor prognosis of digestive tract cancers with low HSPH1, and nominating HSPH1 as a cancer drug target. We propose dual roles of HSPA1 either alone or in complex with HSPH1 and DNAJB1 in promoting quality control of nascent/newly synthesized proteins and cellular thermotolerance.
HostingRepository	PRIDE
AnnounceDate	2021-05-03
AnnouncementXML	Submission_2021-05-02_16:12:41.761.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Guiyou Tian
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	6x(13)C labeled residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2021-03-31 06:31:54	ID requested
⏵ 1	2021-05-02 16:12:42	announced

Dataset with its publication pending

ProteomeXchange project tag: Cancer (B/D-HPP), Biology/Disease-Driven Human Proteome Project (B/D-HPP), Human Proteome Project

submitter keyword: Stress response, Heat shock protein 70, Ubiquitin Proteasome System (UPS), Esophageal cancer

Dieter A. Wolf
contact affiliation	State key Laboratory of Cellular Stress Biology,School of Pharmaceutical Sciences, Xiamen University,China
contact email	dwolf@xmu.edu.cn
lab head
Guiyou Tian
contact affiliation	School of Pharmaceutical Sciences, Fujian Provincial Key Laboratory of Innovative Drug Target Research and Center for Stress Signaling Networks, Xiamen University, Xiamen, Fujian 361102, China
contact email	tian19880912@qq.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD025123
     1. Label: PRIDE project
     2. Name: Dual roles of HSP70 chaperone HSPA1 in quality control of nascent and newly synthesized proteins