PI3K/Akt/mTOR · target hub

SESN3

Sestrin-3 (SESN3)

SESN3 is a Nutrient & amino-acid sensing (TSC/Rag/GATOR) on the PI3K/Akt/mTOR axis. May function as an intracellular leucine sensor that negatively regulates the TORC1 signaling pathway (PubMed:25263562). May also regulate the insulin-receptor signaling pathway through activation of TORC2 (By similarity). This metabolic regulator may also play a role in protecti… It is indexed under "GATOR / CASTOR / Sestrin (amino-acid & stress sensing, selected)" on our pathway page for antibodies, inhibitors, and assay guidance.

Back to pathway overviewSearch: SESN3UniProt (P58005)

Research notes

  • Combine with other genes in the same hub block via genetics or pharmacology to test non-redundant roles of SESN3.
  • Annotate PIK3CA/PTEN and upstream RTK–Ras context when reading p-AKT, mTORC1/2, or lipid outputs.
  • Verify antibody clone, phospho-site, and stimulation; include KD/KO or inhibitor controls.

On the pathway hub (sections)

Genetic lesions & expression context (quick reference)

Type / exampleDomain / context (brief)
Expression contextTissue/cell-type–dependent expression
Rare variantsSporadic variants—require functional validation
Pathway couplingCo-occurs with neighboring nodes on the hub

Naming and prevalence vary by cohort and assay—annotate clinically with COSMIC, ClinVar, OncoKB, and datasheets; research context only.

Assay readouts for SESN3

  • Amino-acid withdrawal/refeed: Rag nucleotide state and mTORC1 lysosomal recruitment.
  • Rheb/TSC: GTP loading or TSC complex IP.
  • Downstream: p-S6K, p-4E-BP1, ULK1 Ser757 (mTORC1 repression marker).
  • Stress: energy deprivation or CASTOR/sestrin manipulations as relevant.

SESN3 experimental notes

Examples below reflect common literature and public resources (e.g., CCLE, DepMap)—validate genotypes, expression, and passage in your own stocks before committing assays.

[1] Cell lines commonly used for SESN3 studies (examples)

  • Tool lines: HEK293T, MEFs, HeLa, HEK293, C2C12—screen by SESN3 expression and pathway context (CCLE/DepMap).
  • Combine with neighbors (DEPDC5, NPRL2, NPRL3, MIOS) via KD/pharmacology to test non-redundancy.
  • Overexpression/rescue in HEK293T supports mechanism and IP workflows.
  • Isogenic/CRISPR models separate pathway dependency from bypass survival.

[2] Cell samples for SESN3 Western blot

  • Whole-cell lysates—optimize RIPA/NP-40 per antibody; phosphatase inhibitors for phospho blots.
  • Stimulation: serum starvation ± insulin/EGF or amino-acid withdrawal/refeed as relevant.
  • Controls: siRNA/shRNA, CRISPR KO, or inhibitors to validate band specificity.
  • Loading: BCA normalization; subcellular fractionation when needed.

[3] Tissue samples for SESN3 Western blot

  • Matched tumor/adjacent frozen tissues after pathology review.
  • Mouse GEMM or xenografts—mind species antibody cross-reactivity.
  • Primary cells/PDCs when ethically approved.
  • FFPE needs specialized extraction; frozen tissue preferred for phospho work.

[4] Cell samples for SESN3 immunoprecipitation

  • Tagged overexpression: HEK293T FLAG/HA-SESN3 for complex capture.
  • Endogenous IP: high-expression lines; often ≥1–5×10⁶ cells per IP.
  • Stimulation: ligand or nutrient treatments enrich interactions—pilot time courses.
  • Controls: isotype IgG, empty vector, KD/KO negatives.

Human tissues and primary cells require ethics/IRB approval; tumors are heterogeneous—record histotype, site, and preservation conditions.

Bypass & related pathways

Models & genetics note

Overexpression vs endogenous SESN3 can differ in dosage, splicing, and compartmentation—in organoids/PDX, record passage, matrix, and drug history.

Quick search presets

SESN3SESN3 antibodyPI3K inhibitormTOR inhibitor

SESN3-related antibodies (keyword-biased)

Adds SESN3 keyword bias atop the PI3K/Akt/mTOR antibody pool—if sparse, use presets above or global search.

Neighboring targets (same hub)

DEPDC5NPRL2NPRL3MIOSWDR24WDR59SEH1LSEC13

External databases & resources

FAQ

This content supports research reagents and pathway education—not medical advice. Annotate mutations, drug indications, and protocols with authoritative databases, datasheets, and institutional oversight.

Last reviewed: 2026-05-18

Related on this site

See the PI3K/Akt/mTOR hub for neighboring nodes and assay guidance—cross-check MAPK, RTK, metabolism, and autophagy pages as needed.

PI3K/Akt/mTOR·MAPK/ERK·Receptor tyrosine kinase·Metabolism