Dataset Information

The Cystatin D Interactome Associated to Systemic Mastocytosis

ABSTRACT: he aim of the project is to characterize qualitatively and quantitatively the interaction of cystatin D in other protein partner and the formation of a complex in whole saliva of patients affected by different forms of systemic mastocytosis (SM), with and without skin involvement. The different composition of the complex could be useful to distinguish patients from healthy subject and the different forms of systemic mastocytosis. Pools of whole saliva from SM (SM-C and SM+C) patients, and from sex/age matched healthy controls were submitted to immunoprecipitation assay using cystatin D antibody followed by SDS-PAGE in reducing conditions, tryptic digestion, and nano-HPLC-high-resolution-MS/MS analysis.

INSTRUMENT(S): LTQ Orbitrap Elite

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Saliva

DISEASE(S): Systemic Mastocytosis

SUBMITTER: Simone Serrao

LAB HEAD: Professor Tiziana Cabras

PROVIDER: PXD042567 | Pride | 2023-10-24

REPOSITORIES: Pride

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Publications

Salivary Cystatin D Interactome in Patients with Systemic Mastocytosis: An Exploratory Study.

Serrao Simone S Contini Cristina C Guadalupi Giulia G Olianas Alessandra A Lai Greca G Messana Irene I Castagnola Massimo M Costanzo Giulia G Firinu Davide D Del Giacco Stefano S Manconi Barbara B Cabras Tiziana T

International journal of molecular sciences 20230927 19

Mastocytosis, a rare blood disorder characterized by the proliferation of clonal abnormal mast cells, has a variegated clinical spectrum and diagnosis is often difficult and delayed. Recently we proposed the cathepsin inhibitor cystatin D-R<sub>26</sub> as a salivary candidate biomarker of systemic mastocytosis (SM). Its C<sub>26</sub> variant is able to form multiprotein complexes (mPCs) and since protein-protein interactions (PPIs) are crucial for studying disease pathogenesis, potential marke ...[more]

PMID: 37834061

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Project description:TFIID and SAGA complexes play a critical role in RNA Polymerase II dependent activated transcription. Although the two regulatory complexes are recruited to promoters by activation domain-interactions, the contribution of the different subunits or the different domains of the individual subunits is not completely understood. Taf9 is a shared subunit in TFIID and SAGA and has an N-terminal H3-like histone fold domain and a highly conserved C-terminal domain, Taf9-CTD. In this study, we have uncovered an essential role for the Taf9-CTD in transcriptional activation. The Taf9-CTD was not essential for the histone-fold mediated interaction with Taf6, SAGA and TFIID integrity or Gcn4 interaction with SAGA. Transcriptome profiling performed under Gcn4 activating conditions showed that the Taf9-CTD is required for expression of ~17% of the yeast genome and provides a coactivator function to recruit TFIID and SAGA complexes to the promoters in vivo during transcriptional activation. Integrated genome-wide data analysis showed that the Taf9-CTD is required for activation of promoters bound by several transcription factors indicating a broad role for Taf9-CTD in promoter occupancy of TFIID or SAGA complexes. Interestingly, only a subset of the promoters seemed to be dependent on the Taf9-CTD for assembly of the pre-initiation complex indicating redundancy in activator targets to assemble PIC in vivo. Together these results indicate that evolutionarily conserved domains in shared subunits of TFIID and SAGA have a pervasive role in genome-wide transcription. This GEO series consists of 14 microarray hybridizations using the Agilent two-color experiment with the Agilent Custom Saccharomyces cerevisiae 8x15k gene expression array. Four biological replicates each for the wild-type (TAF9), the mutant taf9-tCRD2 strain treated or untreated with SM, and the wild-type (TAF9) versus mutant taf9-tCRD2 treated with SM hybridized as dye-swapped replicates. Two biological replicates for wild-type (SPT20) vs spt20D strains treated with SM, and hybridized as dye-swapped replicates to identify the fraction of SAGA dependent genes under amino-acid starvation conditions. The overall aim was to identify genes dependent on the conserved C-terminal region domain of TAF9 and determine their dependence on the SAGA subunit Spt20 for expression.

Dataset Information

The Cystatin D Interactome Associated to Systemic Mastocytosis

Publications

Salivary Cystatin D Interactome in Patients with Systemic Mastocytosis: An Exploratory Study.

Similar Datasets

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