PXD065551

PXD065551 is an original dataset announced via ProteomeXchange.

Title	enChIP Mediated proteome profiling reveals the role of SMAD-p300 regulatory axis in GM2 synthase transcriptional regulation.
Description	Aberrant expression of sialic acid containing glycolipids, or gangliosides and their corresponding synthases have been associated with a variety of cancers. GM2-synthase,the enzyme responsible for the formation of a pro-tumorigenic ganglioside, GM2 is well reported to be overexpressed across various cancer tissues and cell lines. This over-expression of GM2-synthase has been linked with increased migration, invasion and epithelial to mesenchymal transition (EMT) as well as induction of a local and systemic host immune suppression in cancer. Despite only a handful of studies demonstrating an epigenetic mechanism underlying the transcriptional regulation of GM2-synthase gene, the detailed mechanism still remains unclear. Here we identified the total proteome associated with the GM2-synthase promoter through a modified CRISPR-dCas9 based proteome profiling approach by categorizing all the identified proteins leading to a detailed elucidation of the molecular drivers behind GM2-synthase transcription. While the previous study identified an acetylation-dependent de-repression of the transcription factor SP1 causing GM2-synthase activation, the underlying molecular mechanism driving its activation wasn’t clear. This study demonstrated that the histone acetyltransferase (HAT), p300 acts a pivotal factor which on one hand cause acetylation-mediated degradation of SP1, and on the other hand modulates SMAD2/4 to have a direct positive impact on GM2 synthase gene transcription. We identified p300 to have an activator role in GM2 synthase gene transcription through knock out, knock down and over-expression experiments. Furthermore, SP1 degradation, SMAD activation and their DNA binding patterns shows the important role of p300 on SP1 and SMAD complexes. Altogether we have identified SMAD2/4 as an activator complex, p300 as a positive regulator and uncovered a critical p300-SMAD-SP1 regulatory axis in GM2--synthase transcriptional regulation.
HostingRepository	PRIDE
AnnounceDate	2026-03-27
AnnouncementXML	Submission_2026-03-27_05:03:46.156.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Kaushik Biswas
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	Bruker Daltonics timsTOF series

Revision	Datetime	Status	ChangeLog Entry
0	2025-06-27 01:35:04	ID requested
⏵ 1	2026-03-27 05:03:47	announced

10.1096/FJ.202502746R;

submitter keyword: Mass Spectrometry, HAT, SMAD, p300,dCas9, enChIP, CLASP

Kaushik Biswas
contact affiliation	Department of Biological Sciences, Bose Institute, Kolkata, West Bengal, 700091, India
contact email	kbiswas_1@yahoo.com
lab head
Kaushik Biswas
contact affiliation	Professor
contact email	kblabomicsdata@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD065551
     1. Label: PRIDE project
     2. Name: enChIP Mediated proteome profiling reveals the role of SMAD-p300 regulatory axis in GM2 synthase transcriptional regulation.