Dataset Information

Differential UBE2H-CTLH E2-E3 ubiquitylation modulesregulate erythroid maturation

ABSTRACT: The developmentof haematopoietic stem cellsinto mature erythrocytes–erythropoiesis –is a controlled process characterized by cellular reorganisation and drastic reshaping of the proteome landscape.Failure of ordered erythropoiesis isassociated with anaemias and haematological malignancies. Although the ubiquitin (UB) system isa known crucial post-translational regulator in erythropoiesis, how the erythrocyteis reshaped by the UBsystemis poorly understood.Bymeasuringthe proteomiclandscape of in vitrohuman erythropoiesis models, we founddynamic differential expression ofsubunitsof the CTLH E3 ubiquitin ligase complexthat formeddistinctmaturation stage-dependent assemblies of structurally homologous RANBP9-and RANBP10-CTLH complexes.Moreover,protein abundance of CTLH’s cognate E2-conjugating enzyme UBE2H increased during terminal differentiation,which dependedon catalyticallyactive CTLH E3complexes.CRISPR-Cas9 mediated inactivation of all CTLH E3 assemblies by targeting the catalytic subunit MAEA,orUBE2H, triggered spontaneous and accelerated maturationof erythroid progenitor cellsincluding increased heme and haemoglobin synthesis. Thus, the orderly progression of human erythropoiesis is controlled by the assembly of distinct UBE2H-CTLHmodulesfunctioning at different developmental stages.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Mario Oroshi

LAB HEAD: Matthias Mann

PROVIDER: PXD031992 | Pride | 2023-03-11

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	20191226_QX6_OzKa_SA_HUDEP2_MAEA_KO_Cl31_D0_R1.raw	Raw
	20191226_QX6_OzKa_SA_HUDEP2_MAEA_KO_Cl31_D0_R2.raw	Raw
	20191226_QX6_OzKa_SA_HUDEP2_MAEA_KO_Cl31_D0_R3.raw	Raw
	20191226_QX6_OzKa_SA_HUDEP2_MAEA_KO_Cl31_D12_R1.raw	Raw
	20191226_QX6_OzKa_SA_HUDEP2_MAEA_KO_Cl31_D12_R2.raw	Raw

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Publications

Modular UBE2H-CTLH E2-E3 complexes regulate erythroid maturation.

Sherpa Dawafuti D Mueller Judith J Karayel Özge Ö Xu Peng P Yao Yu Y Chrustowicz Jakub J Gottemukkala Karthik V KV Baumann Christine C Gross Annette A Czarnecki Oliver O Zhang Wei W Gu Jun J Nilvebrant Johan J Sidhu Sachdev S SS Murray Peter J PJ Mann Matthias M Weiss Mitchell J MJ Schulman Brenda A BA Alpi Arno F AF

eLife 20221202

The development of haematopoietic stem cells into mature erythrocytes - erythropoiesis - is a controlled process characterized by cellular reorganization and drastic reshaping of the proteome landscape. Failure of ordered erythropoiesis is associated with anaemias and haematological malignancies. Although the ubiquitin system is a known crucial post-translational regulator in erythropoiesis, how the erythrocyte is reshaped by the ubiquitin system is poorly understood. By measuring the proteomic ...[more]

PMID: 36459484

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