PXD040969

PXD040969 is an original dataset announced via ProteomeXchange.

Title	Prenylated PALM2 Promotes the Migration of Esophageal Squamous Cancer Cells through Activating Ezrin
Description	Proteins containing a CAAX motif at the C-terminus can occur prenylation modification and regulate the localization and activity of a series of key regulatory proteins, including RAS superfamily members, heterotrimeric G proteins, nuclear lamina protein, and several protein kinases and phosphatases. However, studies of prenylated proteins in esophageal cancer are limited. Here, we found that paralemmin-2 (PALM2), a potential prenylated protein, was up-regulated and associated with a poor prognosis of patients, through research on large-scale proteomic data of esophageal cancer in our laboratory. The low throughput verification also showed that the expression of PALM2 in esophageal cancer tissues was higher than that in their paired normal esophageal epithelial tissues, and it was generally expressed in the membrane and cytoplasm of esophageal squamous cancer cells (ESCC). PALM2 interacted with the two subunits of farnesyl transferase (FTase), FNTA and FNTB. The FTase inhibitor weakened the membranous location of PALM2 and mutation in the CAAX motif of PALM2 (PALM2C408S) impaired its membranous localization, indicating PALM was prenylated by FTase. Overexpressed PALM2 promoted the migration of cancer cells, whereas PALM2C408S lost this ability. Mechanistically, PALM2 interacted with the N-terminal FERM domain of ezrin of Ezrin/Radixin/Moesin (ERM) family dependent on its prenylation. The mutagenesis indicated that lysine residues K253/K254/K262/K263 in ezrin’s FERM domain and cysteine residue C408 in PALM2’s CAAX motif were important for their interaction and ezrin activation. The knockout of ezrin prevented enhanced cancer cell migration by PALM2 overexpression. PALM2, depending on its prenylation, made ezrin get more membranous distribution and increased the phosphorylation of ezrin Y146 site. In summary, prenylated PALM2 promoted the migration of cancer cells through activating ezrin.
HostingRepository	iProX
AnnounceDate	2023-03-20
AnnouncementXML	Submission_2023-10-26_19:13:18.871.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Liyan Xu
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion ETD

Revision	Datetime	Status	ChangeLog Entry
0	2023-03-20 00:31:18	ID requested
⏵ 1	2023-10-26 19:13:19	announced

Deng DX, Li CY, Zheng ZY, Wen B, Liao LD, Zhang XJ, Li EM, Xu LY, Prenylated PALM2 Promotes the Migration of Esophageal Squamous Cell Carcinoma Cells Through Activating Ezrin. Mol Cell Proteomics, 22(8):100593(2023) [pubmed]

submitter keyword: Prenylation, PALM2, Esophageal squamous cancer cell, Cell migration, Ezrin

Liyan Xu
contact affiliation	Institute of Oncologic Pathology, Shantou University Medical College
contact email	lyxu@stu.edu.cn
lab head
Liyan Xu
contact affiliation	Institute of Oncologic Pathology, Shantou University Medical College
contact email	lyxu@stu.edu.cn
dataset submitter

iProX dataset URI