Proteomics

Dataset Information

0

HAX1 controls mitochondrial proteostasis

ABSTRACT: The relevance of mitochondrial proteostasis for the differentiation and function of hematopoietic and immune cells is unknown. Dissecting the HCLS1-associated protein X-1 (HAX1) –related protein network, we define a functional CLPB-HAX1-PRKD2-HSP27 axis with critical importance for the differentiation of neutrophil granulocytes and thus elucidate molecular mechanisms underlying congenital neutropenia in patients with mutations in HAX1 and CLPB. As shown by SILAC proteomics, CLPB and HAX1 control the balance of protein synthesis and persistence in mitochondria, leading to dysfunction of the respiratory complex 1. Impaired mitochondrial proteostasis is associated with decreased abundance of the serine-threonine kinase PRKD2 and Ser82-phosphorylated HSP27. Cellular defects in HAX1-/- cells can be functionally reconstituted by HSP27. Thus, mitochondrial proteostasis emerges as a critical mechanism governing the differentiation and function of neutrophil granulocytes.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Cell, Cell Culture

DISEASE(S): Neutropenia

SUBMITTER: Marta Murgia  

LAB HEAD: Christoph Klein

PROVIDER: PXD023790 | Pride | 2022-05-19

REPOSITORIES: Pride

Json Xml

Dataset's files

Source:
Action DRS
Fan_et_al_HSP27_IP.7z Other
Fan_et_al_Triple_SILAC_basis_raw.7z Other
Fan_et_al_triple_SILAC_txt.7z Other
HSP27_only_IP_September_txt.7z Other
SRDF_metadata_Fan_et_al.txt Txt
Items per page:
1 - 5 of 5
altmetric image

Publications

The relevance of molecular mechanisms governing mitochondrial proteostasis to the differentiation and function of hematopoietic and immune cells is largely elusive. Through dissection of the network of proteins related to HCLS1-associated protein X-1, we defined a potentially novel functional CLPB/HAX1/(PRKD2)/HSP27 axis with critical importance for the differentiation of neutrophil granulocytes and, thus, elucidated molecular and metabolic mechanisms underlying congenital neutropenia in patient  ...[more]

Similar Datasets

Proteomics the Effect of Fatty Acids in Hepatic Insulin resistance-part2
2019-07-11 | PXD012066 | Pride
Proteomics QuaNCAT analysis comparing proteins synthesized in neurites and soma in ASCL1-iNeurons
2018-10-17 | PXD005059 | Pride
Proteomics Protemics of human cell during HHV-6A reactivation
2020-04-07 | PXD016211 | Pride
Proteomics,Multiomics DDX54 regulates transcriptome dynamics during DNA damage response, pSILAC
2017-06-12 | PXD006093 | Pride
Proteomics The yeast AIF homolog Nde1 integrates metabolic and proteostatic signals on the mitochondrial surface and executes cell death
2019-11-06 | PXD012531 | Pride
Proteomics Multimodal HLA-I genotype regulation by human cytomegalovirus US10 and resulting surface patterning
2024-07-03 | PXD051190 | Pride
Proteomics RNase L activating 2′-5′ oligoadenlyates bind ABCF1, -3 and Decr-1
2023-08-18 | PXD030134 | Pride
Proteomics N-linked glycosylation enrichment for in-depth cell surface proteomics and the classification of diffuse large B-cell lymphoma subtypes
2016-08-25 | PXD000332 | Pride
Proteomics Systematic analysis of protein turnover in primary cells - Part IV
2018-06-08 | PXD008512 | Pride
Proteomics Systematic analysis of protein turnover in primary cells - Part III
2018-06-08 | PXD008513 | Pride