Affinage

STMN1

Stathmin · UniProt P16949

Length
149 aa
Mass
17.3 kDa
Annotated
2026-06-10
100 papers in source corpus 26 papers cited in narrative 26 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 9/9 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

STMN1 (Op18/stathmin) is a phosphorylation-regulated microtubule-destabilizing protein that controls microtubule dynamics during the cell cycle and cell motility (PMID:10675326, PMID:11285281). Structurally, it forms a kinked protofilament-like complex by capping two longitudinally aligned α/β-tubulin heterodimers through its N-terminus, with the C-terminal α-helical domain mediating stable tubulin binding; these features enable both tubulin sequestration and direct recognition of microtubule ends to trigger catastrophe (PMID:10675326). In interphase the abundant cytosolic protein destabilizes microtubules predominantly by direct interaction rather than by tubulin sequestration (PMID:12972559). Its destabilizing activity is switched off by serine phosphorylation: phosphomimetic mutations abolish tubulin binding and destabilization, and a self-reinforcing positive feedback loop exists in which assembled microtubules promote Ser16 hyperphosphorylation (PMID:11179426, PMID:11285281). During mitosis, chromatin-localized regulators converge on STMN1, with Aurora B required for chromatin-induced Ser16 hyperphosphorylation and Polo-like kinase Plx1 recruited to chromatin to drive hyperphosphorylation and permit spindle assembly (PMID:11285281, PMID:16537398). Multiple kinases inactivate STMN1 in distinct signaling contexts: Pak1 phosphorylates Ser16 downstream of Rac1, and Ser25/Ser38 downstream of HGF to route the protein into a Pak1–WAVE2–kinesin complex driving lamellipodia formation; the ASK1–p38 MAPK cascade targets Ser25; and PKC mediates rapid phosphorylation upon T-cell receptor engagement (PMID:14645234, PMID:19162178, PMID:16110469, PMID:1500712). Conversely, PPP1R14B sustains STMN1 phosphorylation and stability via PP1 catalytic subunits, with STMN1 the critical phosphorylation-dependent effector (PMID:36484700). STMN1 is a recurrent oncogenic node: a somatic Q18→E mutation confers transforming and potentiated aneugenic activity by resisting inhibitory phosphorylation (PMID:12242154, PMID:16624860), and it is transcriptionally upregulated by FoxM1 (direct promoter binding) and by mutant gain-of-function p53 while being repressed by wild-type p53 (PMID:33526768, PMID:17663418, PMID:11072234). Beyond microtubule regulation, phospho-STMN1 (Ser25/Ser38) binds GRP78 to support migration, and STMN1 directly binds the Star and Cyp11a1 promoters to drive steroidogenesis (PMID:27130664, PMID:27270953).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 1992 Medium

    Established that STMN1 phosphorylation is a rapid, kinase-specific response to immune-receptor signaling, placing it downstream of defined signaling pathways before its cytoskeletal role was known.

    Evidence 32Pi metabolic labeling, 2D gels, and kinase inhibitors in T-cell receptor and costimulatory activation

    PMID:1472477 PMID:1500712

    Open questions at the time
    • Did not connect phosphorylation to a molecular activity
    • Functional consequence for microtubules not addressed
  2. 2000 High

    Resolved the molecular basis of STMN1 activity, showing it binds two tubulin heterodimers in a curved protofilament-like complex with separable capping (N-terminal) and stability (C-terminal) determinants.

    Evidence Recombinant reconstitution, electron microscopy, and deletion mapping of the Op18:tubulin complex

    PMID:10675326

    Open questions at the time
    • Did not resolve relative contribution of sequestration vs. direct catastrophe in cells
    • Atomic-resolution structure not determined
  3. 2000 Medium

    Linked STMN1 to cell-cycle control, demonstrating wild-type p53 transcriptionally represses STMN1 and that STMN1 overexpression bypasses p53-mediated G2/M arrest.

    Evidence Differential display, promoter reporter assays, p53 knockdown, and cell-cycle analysis

    PMID:11072234

    Open questions at the time
    • Direct p53 binding to the STMN1 promoter not shown
    • Mechanism of arrest bypass not defined
  4. 2001 High

    Defined phosphorylation as the master switch: phosphomimetic mutants lose activity, microtubule assembly itself feeds back to hyperphosphorylate STMN1, and chromatin-recruited Plx1 drives this during spindle assembly.

    Evidence Xenopus egg extract spindle assembly, tubulin-binding chromatography, AAA/EEE mutants, and Plx1 immunodepletion

    PMID:11179426 PMID:11285281

    Open questions at the time
    • Identity of the microtubule-associated Ser16 kinase in the feedback loop not pinned
    • Spatial organization of phosphorylation along the spindle not resolved
  5. 2002 High

    Showed a cancer-derived Q18E mutation has transforming activity, establishing STMN1 dysregulation as causal in oncogenesis rather than merely correlative.

    Evidence Tumor sequencing, NIH/3T3 focus formation, xenograft growth, and tubulin ultrastructure EM

    PMID:12242154

    Open questions at the time
    • Frequency of the mutation across tumors not established
    • Precise structural effect of Q18E on tubulin binding undefined
  6. 2003 High

    Distinguished STMN1's mechanism from neural family members, showing abundant cytosolic Op18 destabilizes microtubules chiefly by direct interaction rather than efficient tubulin sequestration, and identified Pak1/Rac1 as an inactivating kinase axis.

    Evidence CD2 chimera compartment targeting with tubulin quantification; in vitro Pak1 kinase assay and dominant-active Rac1 epistasis

    PMID:12972559 PMID:14645234

    Open questions at the time
    • In vivo balance between the two mechanisms across cell types not quantified
    • Other Rac effectors not excluded
  7. 2006 High

    Identified Aurora B as the chromatin-localized kinase mediating mitotic STMN1 Ser16 hyperphosphorylation and demonstrated that STMN1 overexpression (especially Q18E) is aneugenic while loss does not impair normal division.

    Evidence Aurora B immunodepletion and inhibition in egg extracts; shRNA knockdown and inducible WT/Q18E expression in K562 cells

    PMID:16537398 PMID:16624860

    Open questions at the time
    • Direct vs. indirect Aurora B action on STMN1 not separated
    • Compensatory factors masking knockdown phenotype unidentified
  8. 2006 Medium

    Extended the kinase network to the ASK1–p38 MAPK cascade phosphorylating Ser25, connecting STMN1 to stress signaling.

    Evidence Constitutively active ASK1, p38 inhibitor, and in vitro kinase assays with all four p38 isoforms in PC12 cells

    PMID:16110469

    Open questions at the time
    • Functional output on microtubule dynamics only inferred
    • Single cell model
  9. 2007 Medium

    Showed gain-of-function mutant p53 upregulates STMN1, providing a route by which STMN1 contributes to microtubule-dependent functions and chemoresistance in tumors.

    Evidence siRNA discriminating mutant vs. wild-type p53, STMN1 siRNA, and drug-sensitivity assays in HCC cells

    PMID:17663418

    Open questions at the time
    • Direct mutant-p53 promoter occupancy not demonstrated
    • Single lab
  10. 2009 Medium

    Revealed a microtubule-independent migratory role: HGF-driven Pak1 phosphorylation at Ser25/Ser38 routes STMN1 into a Pak1–WAVE2–kinesin complex enabling WAVE2 transport and lamellipodia formation, and clarified context-specific kinase routing through CDK1 and ERK.

    Evidence Reciprocal Co-IP, siRNA depletion, Pak1 inhibitor, and live-cell imaging; LMP1 gain/loss with cdc2 and ERK Co-IP

    PMID:19048596 PMID:19162178 PMID:19915797

    Open questions at the time
    • Stoichiometry within the Pak1–WAVE2–kinesin complex not defined
    • Direct vs. bridged interactions in Co-IPs not distinguished
  11. 2012 Medium

    Demonstrated cell-cycle-phase-dependent ERK regulation of STMN1 under LMP1, refining how a single upstream oncoprotein tunes STMN1 phosphorylation differently across mitotic phases.

    Evidence LMP1 modulation with cell-cycle synchronization, ERK–Op18 Co-IP, and microtubule polymerization assays in NPC cells

    PMID:22417000

    Open questions at the time
    • Direct ERK phosphosite on STMN1 not mapped
    • Single lab
  12. 2016 Medium

    Identified non-microtubule effector activities: phospho-STMN1 binds GRP78 to sustain migration, and STMN1 directly binds steroidogenic gene promoters to drive progesterone production.

    Evidence Phospho-specific Co-IP and mass spectrometry with migration assays; promoter reporter and ChIP assays in granulosa cells

    PMID:27130664 PMID:27270953

    Open questions at the time
    • Mechanism by which STMN1, a tubulin-binding protein, engages chromatin/promoters unresolved
    • Direct vs. cofactor-mediated promoter binding not separated
  13. 2017 Medium

    Placed STMN1 in an AKT/FOXM1/STMN1 axis driving therapy-induced cancer stem cell enrichment and drug resistance.

    Evidence siRNA and inhibitors against AKT, FOXM1, STMN1 with CSC/EMT/resistance phenotypes in NSCLC, in vitro and in vivo

    PMID:28850563

    Open questions at the time
    • Direct FOXM1 promoter binding not shown in this study
    • Whether STMN1 microtubule activity drives resistance not isolated
  14. 2019 Medium

    Showed STMN1 mediates tumor–stroma crosstalk through HGF/MET, integrating its expression into the hepatic tumor microenvironment.

    Evidence HCC–hepatic stellate cell co-culture, STMN1 gain/loss, crizotinib, and xenografts

    PMID:31785057

    Open questions at the time
    • Molecular events downstream of STMN1 in stellate-cell activation undefined
    • Single lab
  15. 2021 High

    Established direct transcriptional control by FoxM1, confirming promoter binding and a pan-cancer FoxM1–STMN1 proliferative axis.

    Evidence ChIP confirming FoxM1 binding to the STMN1 promoter, knockdown rescue across multiple cancers, and xenografts

    PMID:33526768

    Open questions at the time
    • Co-regulatory inputs at the STMN1 promoter not mapped
    • Phosphorylation status of induced STMN1 not assessed
  16. 2020 Medium

    Identified post-translational stabilization of STMN1 by HN1 via blocked ubiquitination, adding protein-level control to its transcriptional regulation.

    Evidence Co-IP, ubiquitination assay, and HN1/STMN1 gain/loss epistasis with xenografts in thyroid carcinoma

    PMID:33359451

    Open questions at the time
    • E3 ligase normally targeting STMN1 not identified
    • Direct vs. indirect HN1–STMN1 interaction not resolved
  17. 2023 High

    Defined a phosphatase regulatory mechanism, showing PPP1R14B via PP1 catalytic subunits maintains STMN1 phosphorylation and stability, with phosphorylation-deficient STMN1 failing to rescue, establishing STMN1 as the critical effector controlling tubulin acetylation and microtubule stability.

    Evidence Co-IP, WT vs. phospho-deficient STMN1 rescue, α-tubulin acetylation assay, and metastasis models in TNBC

    PMID:36484700

    Open questions at the time
    • How PPP1R14B selectively preserves rather than removes phosphorylation mechanistically unresolved
    • Specific phosphosites stabilized not enumerated
  18. 2024 Medium

    Uncovered an HMGA1 interaction tuning STMN1 phosphorylation and a microtubule-independent p38MAPK/STAT1 migratory program with a Ser16 dephosphorylation feedback loop.

    Evidence Co-IP/LC-MS/MS, phosphosite-specific analysis, p38MAPK inhibitors, and migration assays in NSCLC

    PMID:38385074

    Open questions at the time
    • Direct HMGA1–STMN1 binding interface undefined
    • How STMN1 activates STAT1 mechanistically unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • How STMN1, a cytosolic tubulin-binding protein, accesses and directly binds gene promoters (Star, Cyp11a1) and exerts microtubule-independent transcriptional/migratory functions remains mechanistically unexplained.
  • No structural basis for STMN1 chromatin/promoter engagement
  • Nuclear import mechanism and DNA-binding capacity not established
  • Coupling between phosphorylation state and non-microtubule functions unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 4 GO:0008092 cytoskeletal protein binding 3
Localization
GO:0005829 cytosol 1
Pathway
R-HSA-1640170 Cell Cycle 4 R-HSA-162582 Signal Transduction 3 R-HSA-1643685 Disease 3
Partners
CDK1FOXM1GRP78HMGA1HN1PPP1R14BTUBATUBB
Complex memberships
Op18:tubulin complexPak1-WAVE2-kinesin complex

Evidence

Reading pass · 26 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 Op18/stathmin (STMN1) forms a complex with two longitudinally aligned α/β-tubulin heterodimers in a kinked protofilament-like structure. The N-terminal part of Op18 'caps' tubulin subunits for complex specificity, while the complete C-terminal α-helical domain is necessary and sufficient for stable Op18:tubulin complex formation. Besides sequestering tubulin, the structural features suggest Op18 can specifically recognize microtubule ends to trigger catastrophes. Recombinant expression, electron microscopy with digital image analysis, deletion mapping, biochemical tubulin-binding assays The EMBO journal High 10675326
2001 Phosphorylation of Op18/stathmin at Ser16 by a microtubule-associated kinase activity constitutes a positive feedback loop: microtubule nucleation and assembly (induced by centrosomes, DMSO, or paclitaxel) promotes Op18/stathmin hyperphosphorylation in Xenopus egg extracts and somatic cells, thereby inactivating Op18's microtubule-destabilizing activity. Xenopus egg extract biochemical assays, in vitro MT nucleation, pharmacological MT stabilization (paclitaxel/DMSO), phosphosite identification, somatic cell validation Molecular biology of the cell High 11179426
2001 Op18/stathmin microtubule-destabilizing activity correlates with its ability to bind tubulin and is abolished by phosphorylation-mimicking (Ser→Glu) mutations. Non-phosphorylatable Op18 (AAA) dramatically decreases microtubule length and density in spindle assembly assays. Xenopus polo-like kinase Plx1, recruited to chromatin, is required for chromatin-induced Op18 hyperphosphorylation and normal spindle assembly; depletion of Plx1 inhibits both. Xenopus egg extract spindle assembly assay, affinity chromatography (tubulin binding), phosphomimetic and non-phosphorylatable mutants, Plx1 immunodepletion The Journal of cell biology High 11285281
2003 Pak1 phosphorylates Op18/stathmin specifically at Ser16 in vitro and inactivates its catastrophe-promoting activity. Phosphorylation at either Ser16 or Ser63 alone is sufficient to inhibit Op18 in vitro. Expression of constitutively active Rac1(Q61L) partially overcomes Op18-induced microtubule destabilization in a Pak-dependent manner, placing Op18 inactivation downstream of Rac1→Pak1 signaling. In vitro kinase assay (Pak1 + Op18), time-lapse microscopy microtubule assembly assay, site-directed mutagenesis, constitutively active Rac1 expression in cells, Pak inhibitor experiments The Journal of biological chemistry High 14645234
2006 Aurora B (but not Aurora A) is required for mitotic chromatin-induced hyperphosphorylation of Op18/stathmin at Ser16 in Xenopus egg extracts. Depletion of Aurora B blocks Op18 hyperphosphorylation, and chromatin assembled without Aurora B fails to induce this phosphorylation, placing Aurora B as an essential mediator of chromosome-localized Op18 regulation during spindle assembly. Xenopus egg extract reconstitution, Aurora B immunodepletion, Aurora kinase inhibitor (ZM447439), phosphorylation-site specific assays Proceedings of the National Academy of Sciences of the United States of America High 16537398
2006 Overexpression of wild-type Op18/stathmin causes aneugenic activity (aberrant mitosis, polyploidization, chromosome loss) in K562 leukemia cells, while Op18 depletion does not affect mitotic spindle density or normal cell division. A somatic Q18→E mutation dramatically potentiates aneugenic activity, partly by suppressing phosphorylation-inactivation of Op18's microtubule-destabilizing activity without altering overall phosphorylation status. shRNA-mediated Op18 knockdown, inducible expression of wild-type and Q18E mutant Op18, cell cycle analysis, flow cytometry, microtubule density measurement Molecular biology of the cell High 16624860
2000 p53 negatively regulates stathmin/Op18 expression at the transcriptional level. p53-mediated growth inhibition represses stathmin/Op18 promoter activity, and constitutive overexpression of stathmin/Op18 bypasses p53-mediated G2/M cell cycle arrest. mRNA differential display, reporter gene (promoter) assay, siRNA/antisense knockdown of p53, overexpression of stathmin/Op18, cell cycle analysis International journal of cancer Medium 11072234
2007 Gain-of-function p53 mutations (e.g., p53 Y220C, p53 R213Q) upregulate stathmin/Op18 expression in HCC and other tumor cell types; siRNA knockdown of mutant p53 (but not wild-type p53) reduces stathmin expression. Stathmin siRNA reduces MT-dependent cellular functions (viability, proliferation, migration) and sensitizes HCC cells to paclitaxel, vinblastine, and cisplatin. siRNA knockdown of p53 mutants and wild-type p53, inducible p53-wt expression, stathmin siRNA, cell viability/proliferation/migration assays, drug sensitivity assays Hepatology (Baltimore, Md.) Medium 17663418
2002 A somatic Q18→E mutation in Op18/stathmin (identified in human esophageal adenocarcinoma) confers transforming activity: expression in NIH/3T3 cells causes foci formation and tumor growth in immunodeficient mice, doubles the G2/M fraction, decreases mutant-specific phosphorylation, and alters tubulin ultrastructure. Sequencing of tumor-derived Op18, expression of wild-type vs. Q18E mutant in NIH/3T3 cells, focus formation assay, xenograft tumor growth, cell cycle analysis, electron microscopy of tubulin ultrastructure Cancer cell High 12242154
2003 Op18/stathmin destabilizes interphase microtubules via both tubulin sequestration and direct interaction with microtubules. Unlike neural family members (SCG10, RB3) that strongly sequester tubulin heterodimers at specific cellular compartments, the abundant cytosolic Op18 does not efficiently sequester tubulin at the plasma membrane, indicating Op18 preferentially destabilizes microtubules by direct interaction rather than sequestration. CD2 chimeric fusion proteins for plasma membrane targeting, tubulin heterodimer level quantification, mitotic spindle formation assay, comparison of Op18, SCG10, RB3 chimeras Molecular biology of the cell High 12972559
2006 ASK1-p38 MAP kinase cascade phosphorylates Op18/stathmin, primarily at Ser25, in PC12 cells. All four p38 isoforms phosphorylate Op18 at Ser25 in vitro; in cells, p38α is the dominant mediator. This phosphorylation is upstream of changes in microtubule dynamics. Constitutively active ASK1 expression, 2D electrophoresis phosphorylation analysis, p38 inhibitor (SB203580), in vitro kinase assay with all four p38 isoforms, quantitative RT-PCR for isoform expression Journal of cellular physiology Medium 16110469
2009 Pak1 phosphorylates tubulin-bound STMN1/Op18 at Ser25 and Ser38 in response to HGF stimulation. Phosphorylated STMN1 is recruited to a Pak1-WAVE2-kinesin complex, facilitating WAVE2 transport along microtubules to the leading edge and lamellipodia formation. STMN1 depletion inhibits HGF-induced WAVE2 transport and lamellipodia formation. Pak1 inhibitor (IPA-3), Pak1 siRNA, STMN1 siRNA, co-immunoprecipitation of STMN1 with kinesin-WAVE2 complex, phosphorylation-site specific analysis, live cell imaging of lamellipodia Cellular signalling Medium 19162178
2009 p38/MAPK activation under hypoxia leads to Op18/stathmin dephosphorylation (alongside MAP4 phosphorylation), both contributing to microtubule disruption. Interaction between phospho-p38 and MAP4 was confirmed by co-immunoprecipitation; p38 inhibitor SB203580 increases hypoxic cell viability. Hypoxia treatment of cardiomyocytes and HeLa cells, immunoprecipitation of phospho-p38 and MAP4, p38 inhibitor (SB203580), MKK6(Glu) overexpression, Western blotting of Op18 and MAP4 phosphorylation Cellular and molecular life sciences : CMLS Medium 19915797
2009 EBV-encoded LMP1 upregulates cdc2 (CDK1) kinase activity and promotes phosphorylation of Op18/stathmin, enhancing its interaction with cdc2 and promoting microtubule polymerization during mitosis in NPC cells. Inhibition of LMP1 attenuates the cdc2-Op18 interaction and promotes microtubule depolymerization. LMP1 overexpression/knockdown, co-immunoprecipitation of cdc2 with Op18, cdc2 kinase activity assay, microtubule polymerization assay International journal of cancer Medium 19048596
2012 LMP1 regulates Op18/stathmin through ERK (MAPK) in a cell cycle-dependent manner in NPC cells: LMP1 upregulates ERK phosphorylation during G1/S but negatively regulates ERK phosphorylation during G2/M. Inhibition of LMP1 attenuates ERK-Op18 interaction and promotes microtubule depolymerization. LMP1 expression modulation, cell cycle synchronization, co-immunoprecipitation of ERK with Op18/stathmin, microtubule polymerization assay, ERK/phospho-ERK Western blotting Cancer science Medium 22417000
2016 Phosphorylation of STMN1 at Ser25 and Ser38 (mediated by MEK kinase) is necessary to maintain breast cancer cell migration capabilities. Phospho-STMN1 (pSer25/pSer38) specifically binds GRP78, a novel binding partner; this phosphorylation-dependent interaction is required for STMN1-GRP78 complex stability and STMN1-mediated cell migration. Phosphosite-specific mutants, MEK inhibitor, Co-immunoprecipitation of phospho-STMN1 with GRP78, cell migration assay, mass spectrometry identification of binding partner Cancer letters Medium 27130664
2019 STMN1 mediates crosstalk between hepatocellular carcinoma (HCC) cells and hepatic stellate cells (HSC) via the HGF/MET signaling pathway. HGF secreted by HSCs stimulates STMN1 expression in HCC cells; reciprocally, STMN1 upregulation in HCC cells promotes HSC activation to cancer-associated fibroblast features. MET inhibitor crizotinib blocks this crosstalk. Co-culture of HCC cells with HSCs, STMN1 overexpression/silencing, MET inhibitor (crizotinib) treatment, in vivo xenograft tumor growth, Western blotting of HGF/MET pathway components Cancer science Medium 31785057
2017 TKI treatment activates an AKT/FOXM1/STMN1 pathway in NSCLC cells. FOXM1 transcriptionally upregulates STMN1, contributing to TKI-induced cancer stem cell enrichment and multidrug resistance. Silencing FOXM1 or STMN1, or blocking AKT, reverses TKI-induced resistance. Specific inhibitors and siRNAs targeting AKT, FOXM1, and STMN1, RNA microarray, cell phenotype assays (CSC, EMT, drug resistance), in vitro and in vivo studies British journal of cancer Medium 28850563
2021 FoxM1 transcriptionally upregulates STMN1 (confirmed by ChIP assay). FoxM1 promotes cancer cell proliferation through STMN1 upregulation; a FoxM1-STMN1 axis drives tumorigenesis in hepatocellular carcinoma, gastric cancer, and colorectal cancer. Lentiviral FoxM1/STMN1 knockdown, ChIP assay confirming FoxM1 binding to STMN1 promoter, cell viability/colony formation/soft agar assays, xenograft mouse model, tissue microarray analysis Signal transduction and targeted therapy High 33526768
2023 PPP1R14B (protein phosphatase 1 regulatory subunit 14B) maintains phosphorylation and stability of STMN1 via PP1 catalytic subunits α and γ, promoting TNBC progression and paclitaxel resistance. PPP1R14B deficiency is partially rescued by ectopic wild-type but not phosphorylation-deficient STMN1, establishing STMN1 as the critical downstream effector. PPP1R14B also decreases STMN1-mediated α-tubulin acetylation and microtubule stability. Co-immunoprecipitation, gain/loss-of-function assays, rescue with wild-type vs. phosphorylation-deficient STMN1 mutant, α-tubulin acetylation assay, xenograft and lung metastasis mouse models Cancer research High 36484700
2016 STMN1 promotes progesterone production in mouse granulosa cells by directly binding to and increasing transcriptional activity of the Star (StAR) and Cyp11a1 promoters, as shown by promoter reporter and ChIP assays. STMN1 overexpression stimulates progesterone production; knockdown decreases it. STMN1 overexpression and siRNA knockdown in primary mouse granulosa cells, progesterone measurement, promoter reporter assay, chromatin immunoprecipitation (ChIP) Scientific reports Medium 27270953
2020 HN1 protein interacts with STMN1, increases STMN1 mRNA expression, and prevents STMN1 ubiquitination and proteasomal degradation in anaplastic thyroid carcinoma cells. Loss of STMN1 decreases the malignant potential conferred by HN1; HN1 knockdown with STMN1 overexpression restores aggressive properties. Co-immunoprecipitation, mRNA expression analysis, ubiquitination assay, HN1/STMN1 knockdown and overexpression, xenograft mouse model Cancer letters Medium 33359451
1992 Op18/stathmin (pp19) phosphorylation is rapidly induced within 2 minutes of T cell receptor activation by OKT3 in peripheral blood lymphocytes, and this early phosphorylation is mediated by protein kinase C (blocked by calphostin C), not cyclic nucleotide-dependent kinases. PKC-mediated Op18 phosphorylation precedes S-phase entry. Metabolic 32Pi labeling, 2D gel electrophoresis, PhosphorImager quantification, PKC inhibitor (calphostin C), cyclic nucleotide pathway inhibitors (HA1004, forskolin) Journal of immunology (Baltimore, Md. : 1950) Medium 1500712
1992 Dephosphorylation of pp19 (Op18/stathmin, STMN1) is a common early intracellular event downstream of costimulatory signals (CD2, CD4, CD8 cross-linking with TCR-CD3) in human T cells, and correlates with subsequent IL-2 production and IL-6 responsiveness but not IFN-γ production. Antibody cross-linking of CD2, CD3, CD4, CD8, functional assays (IL-2, IL-6 responsiveness, IFN-γ), phosphoprotein analysis International immunology Medium 1472477
2024 STMN1 interacts with HMGA1 (identified by Co-IP and LC-MS/MS). HMGA1 decreases microtubule stability by regulating STMN1 phosphorylation at Ser16 and Ser38. Additionally, STMN1 promotes NSCLC cell migration by activating the p38MAPK/STAT1 signaling pathway independently of microtubule stability, and p38MAPK activation promotes STMN1 dephosphorylation at Ser16, forming a positive feedback loop. Co-immunoprecipitation, LC-MS/MS, phosphosite-specific analysis, p38MAPK inhibitors, STAT1 pathway analysis, in vitro and in vivo migration assays International journal of biological sciences Medium 38385074
1994 pp19/cofilin (later clarified in the literature as stathmin/Op18, STMN1) undergoes dephosphorylation and subsequent translocation from the cytosol to the nucleus in response to costimulatory signals in T cells, correlating with IL-2 production and proliferation. This nuclear translocation occurs spontaneously in the Jurkat T-lymphoma cell line. Subcellular fractionation, protein identification (Edman sequencing/mass spectrometry noted as Eckerskorn), functional correlation with IL-2 production in primary and Jurkat T cells Proceedings of the National Academy of Sciences of the United States of America Low 8183936

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2016 Lag-3, Tim-3, and TIGIT: Co-inhibitory Receptors with Specialized Functions in Immune Regulation. Immunity 1722 27192565
2018 Fibrinogen-like Protein 1 Is a Major Immune Inhibitory Ligand of LAG-3. Cell 712 30580966
2020 LAG-3: from molecular functions to clinical applications. Journal for immunotherapy of cancer 360 32929051
2023 Targeting LAG-3, TIM-3, and TIGIT for cancer immunotherapy. Journal of hematology & oncology 302 37670328
2018 The promising immune checkpoint LAG-3: from tumor microenvironment to cancer immunotherapy. Genes & cancer 302 30603054
2023 LAG-3 as the third checkpoint inhibitor. Nature immunology 265 37488429
2011 LAG-3 in Cancer Immunotherapy. Current topics in microbiology and immunology 265 21086108
2007 Metalloproteases regulate T-cell proliferation and effector function via LAG-3. The EMBO journal 234 17245433
2018 LAG-3 Inhibitory Receptor Expression Identifies Immunosuppressive Natural Regulatory Plasma Cells. Immunity 212 30005826
2017 CRISPR-Cas9 mediated LAG-3 disruption in CAR-T cells. Frontiers of medicine 204 28625015
2024 LAG-3, TIM-3, and TIGIT: Distinct functions in immune regulation. Immunity 201 38354701
2009 LAG-3 regulates plasmacytoid dendritic cell homeostasis. Journal of immunology (Baltimore, Md. : 1950) 198 19201841
2003 Regulation of microtubule destabilizing activity of Op18/stathmin downstream of Rac1. The Journal of biological chemistry 191 14645234
2019 Lag Phase Is a Dynamic, Organized, Adaptive, and Evolvable Period That Prepares Bacteria for Cell Division. Journal of bacteriology 189 30642990
2000 Spindle assembly and the art of regulating microtubule dynamics by MAPs and Stathmin/Op18. Trends in cell biology 180 10856928
2021 Understanding LAG-3 Signaling. International journal of molecular sciences 166 34067904
2022 The promising immune checkpoint LAG-3 in cancer immunotherapy: from basic research to clinical application. Frontiers in immunology 137 35958563
2017 Tim-3, Lag-3, and TIGIT. Current topics in microbiology and immunology 126 28900677
2003 LAG-3: a regulator of T-cell and DC responses and its use in therapeutic vaccination. Trends in immunology 121 14644131
2011 The CD4-like molecule LAG-3, biology and therapeutic applications. Expert opinion on therapeutic targets 105 21142803
2007 Protumorigenic overexpression of stathmin/Op18 by gain-of-function mutation in p53 in human hepatocarcinogenesis. Hepatology (Baltimore, Md.) 102 17663418
2006 Aurora B is required for mitotic chromatin-induced phosphorylation of Op18/Stathmin. Proceedings of the National Academy of Sciences of the United States of America 93 16537398
2000 Op18/stathmin caps a kinked protofilament-like tubulin tetramer. The EMBO journal 89 10675326
1994 Costimulatory signals for human T-cell activation induce nuclear translocation of pp19/cofilin. Proceedings of the National Academy of Sciences of the United States of America 89 8183936
2022 Clinical landscape of LAG-3-targeted therapy. Immuno-oncology technology 84 35755891
2021 PD-L1/LAG-3 bispecific antibody enhances tumor-specific immunity. Oncoimmunology 81 34239776
2009 Managing jet lag: Some of the problems and possible new solutions. Sleep medicine reviews 80 19147377
2019 STMN1 upregulation mediates hepatocellular carcinoma and hepatic stellate cell crosstalk to aggravate cancer by triggering the MET pathway. Cancer science 78 31785057
2001 Regulation of Op18 during spindle assembly in Xenopus egg extracts. The Journal of cell biology 76 11285281
2022 LAG-3 as a Potent Target for Novel Anticancer Therapies of a Wide Range of Tumors. International journal of molecular sciences 74 36077354
2000 The phosphoprotein Op18/stathmin is differentially expressed in ovarian cancer. Cancer investigation 72 11107442
2009 The p38/MAPK pathway regulates microtubule polymerization through phosphorylation of MAP4 and Op18 in hypoxic cells. Cellular and molecular life sciences : CMLS 71 19915797
2000 p53-mediated negative regulation of stathmin/Op18 expression is associated with G(2)/M cell-cycle arrest. International journal of cancer 69 11072234
2023 Protein Phosphatase 1 Subunit PPP1R14B Stabilizes STMN1 to Promote Progression and Paclitaxel Resistance in Triple-Negative Breast Cancer. Cancer research 66 36484700
2022 LAG-3xPD-L1 bispecific antibody potentiates antitumor responses of T cells through dendritic cell activation. Molecular therapy : the journal of the American Society of Gene Therapy 61 35526096
2022 Cutting-Edge: Preclinical and Clinical Development of the First Approved Lag-3 Inhibitor. Cells 58 35954196
2017 Activation of an AKT/FOXM1/STMN1 pathway drives resistance to tyrosine kinase inhibitors in lung cancer. British journal of cancer 57 28850563
2021 Seven mysteries of LAG-3: a multi-faceted immune receptor of increasing complexity. Immunotherapy advances 55 35265944
2019 On the duration of the microbial lag phase. Current genetics 54 30666394
2020 LAG-3 and PD-1+LAG-3 inhibition promote anti-tumor immune responses in human autologous melanoma/T cell co-cultures. Oncoimmunology 53 32850194
2021 Aberrantly high activation of a FoxM1-STMN1 axis contributes to progression and tumorigenesis in FoxM1-driven cancers. Signal transduction and targeted therapy 52 33526768
2021 PD-1 and LAG-3 blockade improve anti-tumor vaccine efficacy. Oncoimmunology 48 33996265
2020 Progress of immune checkpoint LAG-3 in immunotherapy. Oncology letters 48 32963613
2016 Silencing Op18/stathmin by RNA Interference Promotes the Sensitivity of Nasopharyngeal Carcinoma Cells to Taxol and High-Grade Differentiation of Xenografted Tumours in Nude Mice. Basic & clinical pharmacology & toxicology 46 27289016
2003 Ceramide, stress, and a "LAG" in aging. Science of aging knowledge environment : SAGE KE 46 14523222
2020 Epstein-Barr virus-encoded miR-BART6-3p inhibits cancer cell proliferation through the LOC553103-STMN1 axis. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 45 32306460
2008 Jet lag: therapeutic use of melatonin and possible application of melatonin analogs. Travel medicine and infectious disease 45 18342269
1997 Quantitative analysis of Op18 phosphorylation in childhood acute leukemia. Leukemia 44 9324290
2021 circST6GALNAC6 suppresses bladder cancer metastasis by sponging miR-200a-3p to modulate the STMN1/EMT axis. Cell death & disease 42 33568625
2017 High STMN1 Expression is Associated with Cancer Progression and Chemo-Resistance in Lung Squamous Cell Carcinoma. Annals of surgical oncology 42 28933054
2009 Membrane transport of WAVE2 and lamellipodia formation require Pak1 that mediates phosphorylation and recruitment of stathmin/Op18 to Pak1-WAVE2-kinesin complex. Cellular signalling 41 19162178
2024 Relatlimab: a novel drug targeting immune checkpoint LAG-3 in melanoma therapy. Frontiers in pharmacology 40 38269271
2023 LAG-3 Inhibitors: Novel Immune Checkpoint Inhibitors Changing the Landscape of Immunotherapy. Biomedicines 40 37509517
2016 The phosphorylation-specific association of STMN1 with GRP78 promotes breast cancer metastasis. Cancer letters 40 27130664
2014 Understanding cadherin EGF LAG seven-pass G-type receptors. Journal of neurochemistry 40 25280249
2022 The Role of TIM-3 and LAG-3 in the Microenvironment and Immunotherapy of Ovarian Cancer. Biomedicines 39 36359346
2021 LAG-3 expression in the inflammatory microenvironment of glioma. Journal of neuro-oncology 39 33651248
2020 Lymphocyte Activation Gene (LAG)-3 Is Associated With Mucosal Inflammation and Disease Activity in Ulcerative Colitis. Journal of Crohn's & colitis 39 32179884
2021 Gene of the month: lymphocyte-activation gene 3 (LAG-3). Journal of clinical pathology 38 34183437
2018 miR-423-5p Inhibits Osteosarcoma Proliferation and Invasion Through Directly Targeting STMN1. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 38 30423576
2015 Intensive DNA Replication and Metabolism during the Lag Phase in Cyanobacteria. PloS one 36 26331851
2001 Stathmin/Op18 phosphorylation is regulated by microtubule assembly. Molecular biology of the cell 35 11179426
2020 HN1 promotes tumor growth and metastasis of anaplastic thyroid carcinoma by interacting with STMN1. Cancer letters 34 33359451
2017 Overview of LAG-3-Expressing, IL-10-Producing Regulatory T Cells. Current topics in microbiology and immunology 34 28929191
1995 Immunohistochemical detection of oncoprotein 18 (Op18) in malignant lymphomas. The Histochemical journal 34 7775200
1992 Dephosphorylation of pp19: a common second signal for human T cell activation mediated through different accessory molecules. International immunology 34 1472477
2024 Structural insights reveal interplay between LAG-3 homodimerization, ligand binding, and function. Proceedings of the National Academy of Sciences of the United States of America 33 38483996
2023 A Novel Trojan Horse Nanotherapy Strategy Targeting the cPKM-STMN1/TGFB1 Axis for Effective Treatment of Intrahepatic Cholangiocarcinoma. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 33 37789644
2015 Anti-STMN1 therapy improves sensitivity to antimicrotubule drugs in esophageal squamous cell carcinoma. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 32 25944168
2009 EBV-encoded LMP1 regulates Op18/stathmin signaling pathway by cdc2 mediation in nasopharyngeal carcinoma cells. International journal of cancer 32 19048596
1992 Activation of resting peripheral blood lymphocytes through the T cell receptor induces rapid phosphorylation of Op18. Journal of immunology (Baltimore, Md. : 1950) 32 1500712
2021 LAG-3 Expression Predicts Outcome in Stage II Colon Cancer. Journal of personalized medicine 31 34442393
2020 Chronic shift-lag promotes NK cell ageing and impairs immunosurveillance in mice by decreasing the expression of CD122. Journal of cellular and molecular medicine 30 33185980
2006 Identification of Op18/stathmin as a potential target of ASK1-p38 MAP kinase cascade. Journal of cellular physiology 30 16110469
1983 Cyanogen bromide digestion of the avian myeloblastosis virus pp19 protein: isolation of an amino-terminal peptide that binds to viral RNA. Journal of virology 30 6300441
2020 LAG-3 and GAL-3 in Endometrial Carcinoma: Emerging Candidates for Immunotherapy. International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists 29 32267656
2020 Genomic and immunologic correlates of LAG-3 expression in cancer. Oncoimmunology 29 32923111
2019 Long noncoding RNA TPT1-AS1 downregulates the microRNA-770-5p expression to inhibit glioma cell autophagy and promote proliferation through STMN1 upregulation. Journal of cellular physiology 29 31637705
2024 LAG-3 : recent developments in combinational therapies in cancer. Cancer science 28 38702996
2022 Fewer LAG-3+ T Cells in Relapsing-Remitting Multiple Sclerosis and Type 1 Diabetes. Journal of immunology (Baltimore, Md. : 1950) 28 35022272
2023 Lag-3 expression and clinical outcomes in metastatic melanoma patients treated with combination anti-lag-3 + anti-PD-1-based immunotherapies. Oncoimmunology 27 37808404
2019 Divergent LAG-3 versus BTLA, TIGIT, and FCRL3 expression in Sézary syndrome. Leukemia & lymphoma 27 30638415
2006 Aneugenic activity of Op18/stathmin is potentiated by the somatic Q18-->e mutation in leukemic cells. Molecular biology of the cell 27 16624860
2023 LAG-3 transcriptomic expression patterns across malignancies: Implications for precision immunotherapeutics. Cancer medicine 26 37132280
2021 PTEN loss promotes oncogenic function of STMN1 via PI3K/AKT pathway in lung cancer. Scientific reports 26 34253824
2018 MiR-101 inhibits cell proliferation and invasion of pancreatic cancer through targeting STMN1. Cancer biomarkers : section A of Disease markers 26 30198871
2012 Epstein-Barr virus-encoded LMP1 triggers regulation of the ERK-mediated Op18/stathmin signaling pathway in association with cell cycle. Cancer science 26 22417000
2002 Transforming properties of a Q18-->E mutation of the microtubule regulator Op18. Cancer cell 25 12242154
1992 Differential expression of Op18 phosphoprotein during human thymocyte maturation. The Journal of clinical investigation 25 1401087
2021 Chronic Jet Lag Exacerbates Jejunal and Colonic Microenvironment in Mice. Frontiers in cellular and infection microbiology 24 34141627
2018 High STMN1 Expression Is Associated with Tumor Differentiation and Metastasis in Clinical Patients with Pancreatic Cancer. Anticancer research 24 29374725
2024 STMN1 Promotes Tumor Metastasis in Non-small Cell Lung Cancer Through Microtubule-dependent And Nonmicrotubule-dependent Pathways. International journal of biological sciences 23 38385074
2023 Development of a high-throughput TR-FRET screening assay for LAG-3/FGL1 interaction. SLAS discovery : advancing life sciences R & D 23 37121273
2016 STMN1 Promotes Progesterone Production Via StAR Up-regulation in Mouse Granulosa Cells. Scientific reports 23 27270953
2025 Proximity between LAG-3 and the T cell receptor guides suppression of T cell activation and autoimmunity. Cell 22 40592325
2023 Development of LAG-3/FGL1 blocking peptide and combination with radiotherapy for cancer immunotherapy. Acta pharmaceutica Sinica. B 21 38486998
2016 Elevated STMN1 promotes tumor growth and invasion in endometrial carcinoma. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 21 26815505
2019 Gestational jet lag predisposes to later-life skeletal and cardiac disease. Chronobiology international 20 30793958
2023 Advancement of anti-LAG-3 in cancer therapy. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 19 37846808
2003 Deciphering the cellular functions of the Op18/Stathmin family of microtubule-regulators by plasma membrane-targeted localization. Molecular biology of the cell 19 12972559

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