Functional role of SAP18 protein: From transcriptional repression to splicing regulation

Kumari, Sweta; Rehman, Ayushi; Chandra, Pratap; Singh, Kusum

doi:10.1002/cbf.3830

Cited by 3 publications

(1 citation statement)

References 103 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It also plays a significant role in breast cancer metastasis (4), activating autophagy (5), contributing to pulmonary arterial hypertension (6), and influencing triple-negative breast cancer (7). In addition to the SIN3A/B paralogues, several proteins bind with the Sin/HDAC complexes including RBBP4/RBBP7 and HDAC1/2, which are shared with other transcriptional repressor complexes, and the Sin3-associated proteins SAP30/SAP30L, SUDS3, BRMS1/BRMS1L, ING1/2, ARID4A/B, SAP18, FAM60A, and SAP25 (8)(9)(10)(11). While SIN3/HDACSin3/HDAC complexes mainly regulate gene transcription (12), several by deacetylating histone tails and altering the chromatin environment , components of the Sin3/HDAC complex interact with proteins carrying various enzymatic activities (11,13,14).…”

Section: Introductionmentioning

confidence: 99%

Distinct regions within SAP25 recruit O-linked glycosylation, DNA demethylation, and ubiquitin ligase and hydrolase activities to the Sin3/HDAC complex

Goswami,

Banks,

Thornton

et al. 2024

Preprint

View full text Add to dashboard Cite

Epigenetic control of gene expression is crucial for maintaining gene regulation. Sin3 is an evolutionarily conserved repressor protein complex mainly associated with histone deacetylase (HDAC) activity. A large number of proteins are part of Sin3/HDAC complexes, and the function of most of these members remains poorly understood. SAP25, a previously identified Sin3A associated protein of 25 kDa, has been proposed to participate in regulating gene expression programs involved in the immune response but the exact mechanism of this regulation is unclear. SAP25 is not expressed in HEK293 cells, which hence serve as a natural knockout system to decipher the molecular functions uniquely carried out by this Sin3/HDAC subunit. Using molecular, proteomic, protein engineering, and interaction network approaches, we show that SAP25 interacts with distinct enzymatic and regulatory protein complexes in addition to Sin3/HDAC. While the O-GlcNAc transferase (OGT) and the TET1 /TET2/TET3 methylcytosine dioxygenases have been previously linked to Sin3/HDAC, in HEK293 cells, these interactions were only observed in the affinity purification in which an exogenously expressed SAP25 was the bait. Additional proteins uniquely recovered from the Halo-SAP25 pull-downs included the SCF E3 ubiquitin ligase complex SKP1/FBXO3/CUL1 and the ubiquitin carboxyl-terminal hydrolase 11 (USP11), which have not been previously associated with Sin3/HDAC. Finally, we use mutational analysis to demonstrate that distinct regions of SAP25 participate in its interaction with USP11, OGT/TETs, and SCF(FBXO3).) These results suggest that SAP25 may function as an adaptor protein to coordinate the assembly of different enzymatic complexes to control Sin3/HDAC-mediated gene expression.

show abstract

Section: Introductionmentioning

confidence: 99%

Distinct regions within SAP25 recruit O-linked glycosylation, DNA demethylation, and ubiquitin ligase and hydrolase activities to the Sin3/HDAC complex

Goswami,

Banks,

Thornton

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

Nsp10-interacting host protein SAP18 restricts PEDV replication in Marc-145 cells via enhancing dephosphorylation of RIG-I

Yang,

Zhang,

Wang

et al. 2024

Veterinary Microbiology

View full text Add to dashboard Cite

Machine learning hypothesis-generation for patient stratification and target discovery in rare disease: our experience with Open Science in ALS

Geraci,

Bhargava,

Qorri

et al. 2024

Front. Comput. Neurosci.

View full text Add to dashboard Cite

IntroductionAdvances in machine learning (ML) methodologies, combined with multidisciplinary collaborations across biological and physical sciences, has the potential to propel drug discovery and development. Open Science fosters this collaboration by releasing datasets and methods into the public space; however, further education and widespread acceptance and adoption of Open Science approaches are necessary to tackle the plethora of known disease states.MotivationIn addition to providing much needed insights into potential therapeutic protein targets, we also aim to demonstrate that small patient datasets have the potential to provide insights that usually require many samples (>5,000). There are many such datasets available and novel advancements in ML can provide valuable insights from these patient datasets.Problem statementUsing a public dataset made available by patient advocacy group AnswerALS and a multidisciplinary Open Science approach with a systems biology augmented ML technology, we aim to validate previously reported drug targets in ALS and provide novel insights about ALS subpopulations and potential drug targets using a unique combination of ML methods and graph theory.MethodologyWe use NetraAI to generate hypotheses about specific patient subpopulations, which were then refined and validated through a combination of ML techniques, systems biology methods, and expert input.ResultsWe extracted 8 target classes, each comprising of several genes that shed light into ALS pathophysiology and represent new avenues for treatment. These target classes are broadly categorized as inflammation, epigenetic, heat shock, neuromuscular junction, autophagy, apoptosis, axonal transport, and excitotoxicity. These findings are not mutually exclusive, and instead represent a systematic view of ALS pathophysiology. Based on these findings, we suggest that simultaneous targeting of ALS has the potential to mitigate ALS progression, with the plausibility of maintaining and sustaining an improved quality of life (QoL) for ALS patients. Even further, we identified subpopulations based on disease onset.ConclusionIn the spirit of Open Science, this work aims to bridge the knowledge gap in ALS pathophysiology to aid in diagnostic, prognostic, and therapeutic strategies and pave the way for the development of personalized treatments tailored to the individual’s needs.

show abstract

Functional role of SAP18 protein: From transcriptional repression to splicing regulation

Cited by 3 publications

References 103 publications

Distinct regions within SAP25 recruit O-linked glycosylation, DNA demethylation, and ubiquitin ligase and hydrolase activities to the Sin3/HDAC complex

Distinct regions within SAP25 recruit O-linked glycosylation, DNA demethylation, and ubiquitin ligase and hydrolase activities to the Sin3/HDAC complex

Nsp10-interacting host protein SAP18 restricts PEDV replication in Marc-145 cells via enhancing dephosphorylation of RIG-I

Machine learning hypothesis-generation for patient stratification and target discovery in rare disease: our experience with Open Science in ALS

Contact Info

Product

Resources

About