Affinage

DYNLL1

Dynein light chain 1, cytoplasmic · UniProt P63167

Length
89 aa
Mass
10.4 kDa
Annotated
2026-06-09
100 papers in source corpus 34 papers cited in narrative 34 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DYNLL1 (LC8) is a small, highly conserved homodimeric hub protein that functions as a dimerization engine, binding short linear TQT-anchored motifs in intrinsically disordered regions of diverse partners and thereby driving their dimerization or higher-order oligomerization (PMID:10426949, PMID:26652654, PMID:31266884). The protein exists in a reversible, pH-dependent monomer–dimer equilibrium, and dimerization creates two symmetric hydrophobic grooves at the interface into which a partner peptide inserts as an additional antiparallel beta-strand (PMID:10426949, PMID:11327818). Recognition combines a rigid TQT anchor with flexible flanking contacts, an 'anchored flexibility' mode that explains both the conserved motif requirement and tolerance for sequence diversity, and partner binding can be tuned by phosphorylation immediately N-terminal to the motif (PMID:23482567, PMID:26652654). Through this engine DYNLL1 oligomerizes structurally and functionally unrelated clients, including Nek9, the Ana2 centriole duplication factor, and the Panoramix subunit of the piRNA-pathway PICTS silencing complex, where artificial dimerization fully bypasses the LC8 requirement (PMID:21454704, PMID:24920673, PMID:33538693). In the DNA damage response DYNLL1 directly binds and disrupts the MRE11 dimer to restrain DNA end resection, while also stimulating 53BP1 oligomerization and its recruitment to double-strand-break chromatin to promote NHEJ; together these activities determine repair pathway choice, and DYNLL1 loss restores homologous recombination and PARP-inhibitor resistance in BRCA1-deficient cells (PMID:30464262, PMID:30559443, PMID:37696958, PMID:30982887). DYNLL1 abundance is set by a feedback loop with the transcription factor ASCIZ, which directly activates Dynll1 transcription while DYNLL1 protein binds multivalent motifs in the ASCIZ activation domain to inhibit it; this axis controls Bim-dependent apoptosis in developing B cells and is co-opted in MYC-driven B-cell lymphoma (PMID:22167198, PMID:22891272, PMID:32139510, PMID:26832406). Additional characterized roles include redox-regulated inhibition of NF-κB signaling via IκBα binding and control of osteoclastogenesis, regulation of axonal mitochondrial docking through syntaphilin, and dimerization-dependent nuclear import of Pak1 (PMID:18579519, PMID:23293355, PMID:19641106, PMID:19557173).

Mechanistic history

Synthesis pass · year-by-year structured walk · 32 steps
  1. 1999 High

    Established the structural basis for how DYNLL1 binds partners, answering how a small protein recognizes diverse peptides: the dimer presents grooves that accept a partner peptide as a beta-strand.

    Evidence X-ray crystallography of the LC8 dimer bound to an nNOS peptide

    PMID:10426949

    Open questions at the time
    • Single peptide complex; generality of the binding mode across partners not yet tested
    • No quantitation of dimerization energetics
  2. 2001 High

    Defined DYNLL1 as a reversible, pH-sensitive monomer–dimer system, showing that the functional binding unit is the dimer and can be regulated by the monomer–dimer equilibrium.

    Evidence Analytical ultracentrifugation, SEC, circular dichroism and fluorescence on recombinant LC8

    PMID:11327818

    Open questions at the time
    • Physiological relevance of pH-dependent dissociation in cells unaddressed
    • Does not link equilibrium state to specific partner binding outcomes
  3. 2007 High

    Reframed DYNLL1 from a dynein cargo adaptor to a general dimerization engine by showing cargo peptides bind the same groove with higher affinity than dynein intermediate chain.

    Evidence Crystallography, hydrogen-exchange NMR, and ITC comparing dynein IC and Swallow peptides

    PMID:17570393

    Open questions at the time
    • Functional consequence of dimerization tested only in vitro for these partners
    • Did not enumerate the full client repertoire
  4. 2008 High

    Linked DYNLL1 to redox-controlled NF-κB signaling, explaining how oxidative stress relieves DYNLL1's inhibition of IκBα phosphorylation.

    Evidence Co-IP, NF-κB reporter assays, and redox biochemistry showing Cys2 disulfide formation reversed by TRP14

    PMID:18579519

    Open questions at the time
    • Stoichiometry of the LC8–IκBα complex not defined
    • In vivo significance of the redox switch not established
  5. 2008 High

    Resolved how DYNLL1 engages Pak1, refuting a phosphorylation model and showing binding occurs in the canonical groove requiring dimerization.

    Evidence NMR, crystallography, LC8 point mutants, and in vitro kinase assay

    PMID:18650427

    Open questions at the time
    • Cellular consequence of Pak1 binding not directly tested in this study
    • Whether binding alters Pak1 catalytic activity unresolved
  6. 2008 Medium

    Connected DYNLL1 to nNOS activity-state and compartmentalization, indicating it associates selectively with catalytically inactive, phosphorylated cytosolic nNOS.

    Evidence Co-IP, subcellular fractionation, and in vitro NO assay in mouse gut nitrergic varicosities

    PMID:18635601

    Open questions at the time
    • Direct binding interface to nNOS not mapped here
    • Proposed membrane-transport role inferred, not demonstrated
  7. 2009 High

    Demonstrated DYNLL1 controls axonal mitochondrial docking by enhancing the syntaphilin–microtubule interaction, extending the dimerization-engine concept to organelle positioning.

    Evidence Co-IP, motif-deletion mutagenesis, live imaging in neurons, and CD on the SNPH coiled-coil

    PMID:19641106

    Open questions at the time
    • Whether DYNLL1 oligomerizes SNPH per se not directly shown
    • Regulation of the interaction in vivo unaddressed
  8. 2009 Medium

    Tied DYNLL1-mediated Pak1 dimerization to a functional outcome: EGF-induced nuclear import of Pak1 and developmental rescue.

    Evidence Fluorescence import assays in MCF-7 cells and zebrafish morpholino rescue with binding/NLS mutants

    PMID:19557173

    Open questions at the time
    • Single-lab finding without reciprocal structural validation in cells
    • Mechanism connecting dimerization to NLS exposure not defined
  9. 2011 High

    Established the ASCIZ–DYNLL1 transcriptional feedback loop, explaining how cellular DYNLL1 levels are homeostatically set.

    Evidence ChIP, promoter reporter, and co-IP across human, mouse, and chicken cells

    PMID:22167198

    Open questions at the time
    • Quantitative threshold of DYNLL1 needed to inhibit ASCIZ unclear
    • Other transcriptional inputs to Dynll1 not explored
  10. 2011 High

    Showed DYNLL1 binding multimerizes Nek9 and inserts a phospho-regulated switch into spindle-kinase signaling.

    Evidence Co-IP, kinase activity assays, mutagenesis, and SEC on the Nek9/Nek6 module

    PMID:21454704

    Open questions at the time
    • Cellular spindle phenotypes of disrupting the interaction not detailed here
  11. 2011 Medium

    Mapped DYNLL1 binding to multiple SQ/TQ motifs in ATMIN/ASCIZ and showed reciprocal effects on localization, supporting the multivalent feedback model.

    Evidence Yeast two-hybrid, pepscan, NMR-modeled complexes, and co-expression imaging

    PMID:21971545

    Open questions at the time
    • Binding stoichiometry resolved only later
    • Functional consequence on transcription not measured here
  12. 2012 High

    Placed DYNLL1 downstream of ASCIZ in B-cell development by genetic epistasis, showing the lymphopenia of ASCIZ loss runs through DYNLL1 and Bim-dependent apoptosis.

    Evidence Ectopic Dynll1 rescue and Bim-knockout epistasis with flow cytometry in mice

    PMID:22891272

    Open questions at the time
    • Direct DYNLL1 control of Bim at the molecular level not dissected here
  13. 2012 Medium

    Implicated DYNLL1 in microtubule assembly and mitotic spindle stability, broadening its cytoskeletal roles.

    Evidence In vitro MT assembly, immunofluorescence in Drosophila and HeLa, siRNA/overexpression, docking

    PMID:23038268

    Open questions at the time
    • Direct tubulin-binding interface unresolved
    • Single-lab, not independently replicated
  14. 2013 High

    Provided the structural mechanism for phosphorylation-gated partner binding, showing pSer944 immediately N-terminal to the Nek9 motif weakens LC8 affinity.

    Evidence Crystal structures of phosphorylated/unphosphorylated peptides plus ITC

    PMID:23482567

    Open questions at the time
    • Generality of N-terminal phospho-regulation across other partners not surveyed
  15. 2013 Medium

    Extended DYNLL1's NF-κB-inhibitory role to osteoclast biology and bone homeostasis in vivo.

    Evidence Osteoclast differentiation assays, Western blots, LC8-transgenic mice, ovariectomy model

    PMID:23293355

    Open questions at the time
    • Single lab; direct binding partners in the MAPK arm not mapped
    • Mild phenotype leaves contribution magnitude uncertain
  16. 2014 High

    Demonstrated DYNLL1 builds defined higher-order assemblies, dimers bridging two Ana2 sites to drive Ana2 tetramerization in centriole duplication.

    Evidence Two crystal structures, SEC-MALS stoichiometry, and ITC

    PMID:24920673

    Open questions at the time
    • Cellular requirement for the tetramer in centriole duplication inferred from structure
  17. 2014 Medium

    Implicated DYNLL1 with Arl3-GTP in regulating dynein–dynactin association, retaining a connection to the motor system.

    Evidence Co-IP, MT pull-down, quantum-dot tracing, live imaging, siRNA

    PMID:25342295

    Open questions at the time
    • Mechanism by which LC8 promotes dynactin detachment not structurally defined
    • Single lab
  18. 2015 High

    Defined the 'anchored flexibility' recognition model reconciling the strict TQT requirement with broad sequence tolerance among partners.

    Evidence Crystallography of a Chica peptide complex with NMR dynamics and ITC

    PMID:26652654

    Open questions at the time
    • Predictive power across the proteome addressed only by later screening
  19. 2015 Medium

    Showed viral proteins exploit DYNLL1 as a dimerization cofactor, with VP35 binding stabilizing its oligomerization domain to enhance viral RNA synthesis.

    Evidence Direct binding, Ebola minigenome assay, and VP35 motif mutagenesis

    PMID:25741013

    Open questions at the time
    • Structural detail of the VP35–LC8 complex not resolved here
    • Single lab
  20. 2018 High

    Revealed DYNLL1 as a direct inhibitor of DNA end resection, binding MRE11 and limiting nucleolytic processing to enforce repair pathway choice.

    Evidence CRISPR loss-of-function screen, in vitro end-resection biochemistry, co-IP, HR/NHEJ assays

    PMID:30464262

    Open questions at the time
    • Mechanism of MRE11 inhibition resolved structurally only later
    • Interplay with shieldin not yet defined here
  21. 2018 High

    Showed DYNLL1 organizes 53BP1 oligomers to promote NHEJ and class switch recombination, and that its loss confers PARP-inhibitor resistance in BRCA1-mutant cells.

    Evidence Co-IP, CSR assays, Dynll1/Asciz deletion, 53BP1 oligomerization and PARPi sensitivity in cells and tumors

    PMID:30559443

    Open questions at the time
    • Stoichiometry of 53BP1 oligomers in chromatin not defined
  22. 2019 High

    Placed DYNLL1 within the canonical DSB signaling cascade, showing its 53BP1-dependent recruitment to damage tracks and checkpoint function.

    Evidence Laser micro-irradiation, genetic inactivation, checkpoint readouts, PARPi sensitivity

    PMID:30982887

    Open questions at the time
    • Direct chromatin-binding versus 53BP1-mediated recruitment not fully separated
  23. 2019 High

    Demonstrated the dimerization-engine function in the piRNA pathway, where artificial dimerization of Panoramix bypasses the LC8 requirement for transposon silencing.

    Evidence Ctp knockout, artificial dimerization rescue, co-IP, and tethering assays in Drosophila

    PMID:33538693

    Open questions at the time
    • Whether mammalian DYNLL1 has an analogous silencing client unaddressed
  24. 2019 Medium

    Showed DYNLL1 reshapes a viral phosphoprotein's conformational ensemble, restricting RavP domain orientation toward an active polymerase-cofactor state.

    Evidence NMR, SAXS, modeling, rabies minigenome assay, co-localization

    PMID:31634467

    Open questions at the time
    • Functional model based on ensemble inference; single lab
  25. 2019 Medium

    Systematically mapped the human LC8 interactome and built a predictive motif algorithm, confirming the TQT anchor with flanking-residue determinants.

    Evidence Proteomic phage display with ITC validation of 29 peptides and LC8Pred development

    PMID:31266884

    Open questions at the time
    • Predicted partners require individual functional validation
    • Prediction accuracy ~78%
  26. 2020 Medium

    Resolved how DYNLL1 multivalently engages ASCIZ, binding in-register across its three motifs with linker length and motif specificity governing the mode.

    Evidence NMR, AUC, native ESI-MS, and STD-NMR on the ASCIZ IDP domain

    PMID:32139510

    Open questions at the time
    • Single lab; in-register binding consequences for transcriptional output not measured
  27. 2020 High

    Refined the resection mechanism, showing DYNLL1 disrupts the MRE11 dimer and coordinates timing with shieldin recruitment at breaks.

    Evidence Co-IP, DSB localization, cell-cycle analysis, PARPi sensitivity

    PMID:37696958

    Open questions at the time
    • Structure of the DYNLL1–MRE11 complex not solved here
  28. 2020 Medium

    Identified a mitochondrial DYNLL1–Cox4i1 complex acting as a brake on ROS, dissociated upon pathogen infection to control bacterial proliferation.

    Evidence Mass spectrometry, co-IP, ROS and bacterial proliferation assays in dendritic cells

    PMID:32041786

    Open questions at the time
    • Whether this depends on canonical TQT-motif binding unknown
    • Single lab
  29. 2021 High

    Established the ASCIZ–DYNLL1 axis as a driver of MYC-induced B-cell lymphoma, with co-activation by ASCIZ and MYC and a tumor-promoting, apoptosis-restraining role.

    Evidence Constitutive and inducible Asciz/Dynll1 deletion in Eµ-Myc mice with flow cytometry and apoptosis assays

    PMID:26832406

    Open questions at the time
    • Whether DNA-repair versus apoptotic functions dominate tumorigenesis not separated
  30. 2018 High

    Showed isoform-selective dimerization of a myelin glycoprotein, with DYNLL1 forming a 2:2 heterotetramer dimerizing L-MAG but not S-MAG.

    Evidence Yeast two-hybrid, in vitro binding, crystallography, and SAXS

    PMID:30261098

    Open questions at the time
    • Cellular consequence for myelin-to-axon signaling not directly tested
  31. 2022 Medium

    Defined post-translational control of DYNLL1 stability, identifying RNF114-mediated ubiquitination antagonized by DLEU1 lncRNA in esophageal carcinoma.

    Evidence RNA pulldown, co-IP, ubiquitination assay, siRNA, xenografts

    PMID:35619131

    Open questions at the time
    • Direct RNF114 ubiquitination site on DYNLL1 not mapped
    • Single lab
  32. 2005 Low

    Reported an early DYNLL1–PAX6 interaction with patient mutations weakening binding, hinting at relevance to PAX6-dependent development.

    Evidence Yeast two-hybrid library screen and PAX6 patient-allele mutagenesis

    PMID:16098226

    Open questions at the time
    • Yeast two-hybrid only, no orthogonal validation
    • No mechanistic or in vivo follow-up

Open questions

Synthesis pass · forward-looking unresolved questions
  • How DYNLL1's competing roles across DNA repair, transcriptional feedback, cytoskeleton, and organelle/redox control are partitioned and prioritized within a single cell remains unresolved.
  • No model integrating partner competition for the limited groove pool
  • No structure of the DYNLL1–MRE11 complex
  • Quantitative rules governing which clients dominate at given DYNLL1 levels unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 4 GO:0098772 molecular function regulator activity 4 GO:0008092 cytoskeletal protein binding 2
Localization
GO:0005634 nucleus 3 GO:0005739 mitochondrion 2 GO:0005829 cytosol 2 GO:0005856 cytoskeleton 1
Pathway
R-HSA-73894 DNA Repair 4 R-HSA-162582 Signal Transduction 2 R-HSA-5357801 Programmed Cell Death 2 R-HSA-74160 Gene expression (Transcription) 2 R-HSA-8953854 Metabolism of RNA 1
Partners
53BP1ANA2ASCIZIΚBΑMRE11NEK9PAK1SNPH
Complex memberships
53BP1 oligomeric complexMRN complex (with MRE11)Nek9/Nek6/7 spindle kinase modulePICTS complex (Panoramix-Nxf2-Nxt1)

Evidence

Reading pass · 34 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 Crystal structure of PIN/LC8 (DYNLL1) dimer reveals two monomers forming a rectangular dimer with two pairs of alpha-helices covering opposite faces, each packing against a five-stranded antiparallel beta-sheet (four strands from one monomer, one from the other). A 13-residue nNOS peptide binds in a deep hydrophobic groove at the dimer interface as a sixth antiparallel beta-strand, providing structural basis for dimerization and peptide binding. X-ray crystallography Nature structural biology High 10426949
2001 LC8 (DYNLL1) exists as a reversible monomer-dimer equilibrium with a dissociation constant of ~12 µM at pH 7; dimerization is pH-dependent, with dissociation to monomer below pH ~4.8, attributable to titration of a histidine pair at the dimer interface. Unfolding is a two-stage process: dimer dissociation to folded monomer precedes global unfolding. Analytical ultracentrifugation, size-exclusion chromatography, circular dichroism, fluorescence spectroscopy Biochemistry High 11327818
2007 LC8 (DYNLL1) binds peptides from both dynein intermediate chain (IC) and the Drosophila cargo protein Swallow (Swa) in the same grooves at the dimer interface; both GIQVD and KXTQT fingerprint sequences are recognized in the same groove. Swallow binds with higher affinity than IC, suggesting that LC8's binding to cargo proteins like Swallow serves a dimerization function independent of its role in dynein. X-ray crystallography, hydrogen isotope exchange NMR, isothermal titration calorimetry Journal of molecular biology High 17570393
2008 DYNLL1 (LC8) binds IκBα and prevents its phosphorylation by IκB kinase (IKK), thereby inhibiting NF-κB activation. TNFα-induced reactive oxygen species oxidize LC8 to form an intermolecular disulfide bond between Cys2 residues, causing LC8 dissociation from IκBα. The thioredoxin-related protein TRP14 reduces oxidized LC8 to maintain its inhibitory function. Co-immunoprecipitation, in-cell NF-κB reporter assays, redox biochemistry, mutagenesis The Journal of biological chemistry High 18579519
2008 Pak1 (residues 212-222) binds DYNLL1 (LC8) in the same canonical groove as nNOS and BimL, requiring the target-binding interface formed by LC8 dimerization. In vitro phosphorylation assays show Pak1 does not phosphorylate LC8 at Ser88 (which is inaccessible in the dimer), refuting the prior model; instead LC8 binding may modulate Pak1 activity and/or nuclear localization. NMR, X-ray crystallography, biochemical LC8 point mutants (K36P, T67A), in vitro phosphorylation assay The Journal of biological chemistry High 18650427
2008 Phosphomimetic mutation in LC8 (DYNLL1) promotes dissociation to monomer and, by NMR backbone relaxation, the monomer shows more heterogeneous dynamics in residues forming the binding groove (beta1 and beta3 strands), suggesting dimerization pre-organizes the binding groove for ligand recognition. Peptide binding either retains (IC peptide) or silences (Swallow peptide) millisecond-microsecond dynamics in the groove, indicating ligand-specific conformational dynamics. 15N NMR relaxation, equilibrium unfolding Biochemistry Medium 18942858
2009 LC8 (DYNLL1) binds syntaphilin (SNPH) through a seven-residue LC8-binding motif, recruits to axonal mitochondria via SNPH, and enhances the SNPH-microtubule docking interaction to reduce mitochondrial mobility. Deletion of the LC8-binding motif on SNPH abolishes colocalization and impairs SNPH's ability to immobilize mitochondria. Circular dichroism shows LC8 stabilizes an alpha-helical coiled-coil in the SNPH microtubule-binding domain. Co-immunoprecipitation, mutagenesis, time-lapse live imaging in neurons, circular dichroism, fractionation The Journal of neuroscience High 19641106
2009 LC8 (DYNLL1) interaction with Pak1 is required for EGF-induced nuclear import of Pak1 in MCF-7 cells, and this event is contingent on LC8-mediated Pak1 dimerization. Pak2, which lacks an LC8 binding site, remains cytoplasmic upon EGF stimulation. In zebrafish, developmental defects caused by Pak morpholino knockdown are partially rescued by wild-type Pak1 but not by Pak1 mutants disrupting either the LC8 binding or NLS sites. Fluorescence microscopy for nuclear import, zebrafish morpholino rescue, mutagenesis PloS one Medium 19557173
2011 ASCIZ (ATMIN/ZNF822) is a transcriptional activator of the Dynll1 gene; DYNLL1 levels are reduced ~10-fold in ASCIZ-deficient human, mouse, and chicken cells. ASCIZ binds directly to the Dynll1 promoter in a Zn-finger-dependent manner. DYNLL1 protein in turn interacts with ten binding sites in the ASCIZ transcription activation domain, and high DYNLL1 levels inhibit ASCIZ transcriptional activity, forming a feedback loop. DYNLL1 is also required for DNA-damage-induced ASCIZ focus formation. ChIP, promoter reporter assay, co-IP, cell-based transcription assays across three cell types The Journal of biological chemistry High 22167198
2011 LC8 (DYNLL1) binds Nek9 via a (K/R)XTQT motif adjacent to the Nek9 C-terminal coiled coil, causing Nek9 multimerization and increased Nek9 autoactivation. LC8 binding is regulated by Nek9 autophosphorylation on Ser944 immediately N-terminal to the motif. LC8 bound to Nek9 interferes with Nek9's interaction with its downstream partner Nek6 and with Nek6 activation, thus controlling signal transduction through the Nek9/Nek6/7 spindle kinase module. Co-immunoprecipitation, kinase activity assays, mutagenesis, size-exclusion chromatography The Journal of biological chemistry High 21454704
2011 LC8 (DYNLL1) binds to multiple SQ/TQ motifs in the C-terminal domain of ATMIN/ASCIZ; co-expression of mCherry-DYNLL1 and GFP-ATMIN mutually affects intracellular protein localization, and DYNLL1 partially impedes DNA damage-induced ATMIN nuclear foci formation. Yeast two-hybrid, pepscan, NMR-modelled complexes, co-expression localization imaging Biochemical and biophysical research communications Medium 21971545
2012 DYNLL1 (LC8) regulates B cell development downstream of ASCIZ: ASCIZ-deficient B cell precursors have highly reduced DYNLL1 levels, and ectopic Dynll1 expression restores normal B cell development. The B cell lymphopenia caused by ASCIZ absence can be fully suppressed by deletion of the proapoptotic DYNLL1 target Bim, placing DYNLL1 upstream of Bim-dependent apoptosis in developing B cells. Genetic rescue (ectopic Dynll1 expression), genetic epistasis (Bim knockout), flow cytometry of B cell populations in mice The Journal of experimental medicine High 22891272
2012 LC8 (DYNLL1) binds tubulin, promotes microtubule assembly in vitro, and stabilizes microtubules in Drosophila embryos and HeLa cells. LC8 overexpression increases microtubule acetylation and resistance to cold/nocodazole-induced depolymerization; LC8 knockdown or inhibitory peptides destabilize microtubules, inhibit bipolar spindle assembly, and cause mitotic block in HeLa cells. In vitro microtubule assembly assay, immunofluorescence in Drosophila embryos and HeLa cells, siRNA knockdown, overexpression, molecular docking The Journal of biological chemistry Medium 23038268
2013 Crystal structures of DYNLL1 (LC8) bound to Nek9 binding region peptides with and without phosphorylation on Ser944 reveal that phosphorylation of Ser944 (immediately N-terminal to the KXTQT motif) sterically and electrostatically reduces binding affinity of Nek9 to LC8, providing a structural mechanism for phosphorylation-regulated LC8-partner complex formation. X-ray crystallography, isothermal titration calorimetry, biophysical binding assays The Journal of biological chemistry High 23482567
2013 LC8 (DYNLL1) inhibits RANKL-induced osteoclast differentiation, actin ring formation, and bone resorption by binding IκBα and preventing its phosphorylation and degradation, thereby suppressing NF-κB activation. LC8 also inhibits RANKL-induced JNK and ERK activation and downstream c-Fos and NFATc1 expression. LC8-transgenic mice show a mild osteopetrotic phenotype. Osteoclast differentiation assays, Western blotting, transgenic mouse phenotyping, ovariectomy bone loss model Journal of immunology Medium 23293355
2014 DYNLL1 (LC8) mediates oligomerization of the Ana2 centriole duplication factor by binding two LC8-binding sites within Ana2; site 1 contains a TQT motif (Kd ~1.1 µM) and site 2 a TQC motif (Kd ~13 µM). Crystal structures show the Ana2 peptides form beta-strands extending a central LC8 beta-sandwich. LC8 dimers binding two Ana2 sites induce Ana2 tetramerization, yielding an Ana2M4-LC88 complex. X-ray crystallography (two independent structures), size-exclusion chromatography-multiangle light scattering, isothermal titration calorimetry, mutagenesis The Journal of biological chemistry High 24920673
2014 Arl3 (GTP-bound) and LC8 (DYNLL1) together induce dissociation of dynactin from dynein. Immunoprecipitation and microtubule pull-down assays showed Arl3(Q71L) and LC8 facilitate dynactin detachment from dynein. LC8 interacts with dynein and Arl3 interacts with dynactin. siRNA knockdown of Arl3 and LC8 causes abnormal localizations of dynein, dynactin, and related organelles. Co-immunoprecipitation, microtubule pull-down, quantum dot-conjugated protein tracing, live-cell imaging, siRNA knockdown Nature communications Medium 25342295
2015 Crystal structure of DYNLL1 (LC8) bound to a Chica spindle-adaptor peptide identifies a rigid TQT-LC8 anchor interaction coupled with flexible non-TQT interactions, establishing an 'anchored flexibility' model of LC8 motif recognition that explains both TQT requirement and sequence diversity tolerance. X-ray crystallography, NMR chemical shift/relaxation, isothermal titration calorimetry Biochemistry High 26652654
2015 Ebola virus VP35 directly and with high affinity interacts with LC8 (DYNLL1). LC8 binding stabilizes the VP35 N-terminal oligomerization domain and enhances viral RNA synthesis. Mutational analysis of VP35 demonstrates the interaction is required for the functional effects of LC8 on RNA synthesis. Direct binding assay, minigenome viral RNA synthesis assay, mutagenesis of VP35 LC8-binding motif Journal of virology Medium 25741013
2018 DYNLL1 is an inhibitor of DNA end resection: identified by CRISPR loss-of-function screen, DYNLL1 loss enables DNA end resection and restores homologous recombination in BRCA1-mutant cells. In vitro, DYNLL1 directly binds MRE11 to limit its end-resection activity. In cells, DYNLL1 associates with the MRN complex, BLM helicase, and DNA2 endonuclease to limit nucleolytic degradation of DNA ends. CRISPR loss-of-function screen, in vitro biochemical end-resection assay, co-immunoprecipitation, HR and NHEJ repair assays Nature High 30464262
2018 DYNLL1 organizes multimeric 53BP1 complexes: DYNLL1 binding stimulates 53BP1 oligomerization and promotes 53BP1 recruitment to DSB-associated chromatin. DYNLL1 regulates 53BP1-dependent NHEJ including immunoglobulin class switch recombination (CSR); deletion of Dynll1 or its regulator Asciz, or mutation of DYNLL1 binding motifs in 53BP1, compromises CSR and renders Brca1 mutant cells resistant to PARP inhibitors. Co-immunoprecipitation, CSR assays, genetic deletion (Dynll1, Asciz), PARP inhibitor sensitivity assays in cells and tumors, 53BP1 oligomerization assay Nature communications High 30559443
2018 DYNLL1 forms a high-affinity heterotetramer with the large myelin-associated glycoprotein (L-MAG) cytoplasmic domain; crystal structure shows 2:2 binding in a parallel arrangement. The DYNLL1-binding segment is near the L-MAG C-terminus adjacent to the Fyn kinase phosphorylation site. DYNLL1 dimerizes L-MAG but not S-MAG, implying an isoform-specific role in myelin-to-axon signaling. Yeast two-hybrid, in vitro binding with recombinant proteins, X-ray crystallography, small-angle X-ray scattering Journal of neurochemistry High 30261098
2019 LC8 (DYNLL1) accumulates at laser-induced DNA damage tracks in a 53BP1-dependent manner, requiring the canonical H2AX-MDC1-RNF8-RNF168 signal transduction cascade. Genetic inactivation of LC8 or its interaction with 53BP1 causes checkpoint defects. Loss of LC8 alleviates hypersensitivity of BRCA1-depleted cells to ionizing radiation and PARP inhibition. Laser micro-irradiation and live-cell imaging, genetic inactivation (siRNA/CRISPR), checkpoint assays (γH2AX, Chk2 phosphorylation), PARP inhibitor sensitivity Nucleic acids research High 30982887
2019 LC8/DYNLL1 (Drosophila Cut-up) is an essential component of the PICTS complex (Panoramix-Nxf2-Nxt1) required for piRNA-pathway co-transcriptional transposon silencing. LC8 drives PICTS complex dimerization through interaction with conserved motifs in Panoramix. Artificial dimerization of Panoramix bypasses the requirement for Ctp/LC8, demonstrating that LC8's role is to promote complex dimerization. Genetic knockout (loss of Ctp causes transposon de-repression and loss of H3K9me3 marks), artificial dimerization rescue, co-immunoprecipitation, tethering assay eLife High 33538693
2019 LC8/DYNLL1 (rabies virus context) binds the disordered linker of the rabies virus phosphoprotein RavP adjacent to an endogenous dimerization domain, restricting RavP domain orientations and inducing a conformation similar to a more active viral polymerase cofactor state. LC8 interactions are essential for efficient viral polymerase functionality; RavP and LC8 colocalize in rabies-infected cells. NMR, SAXS, molecular modeling, viral minigenome assay, co-localization imaging Journal of molecular biology Medium 31634467
2019 Phage display proteomic screen identifies 29 validated LC8 (DYNLL1) binding partners from the human proteome; all validated peptides contain the canonical TQT motif anchor. Residues outside the TQT anchor critically determine binding, enabling development of the LC8Pred algorithm with ~78% accuracy for predicting LC8-binding motifs. Proteomic phage display, isothermal titration calorimetry validation of 29 peptides, bioinformatic algorithm development Life science alliance Medium 31266884
2020 DYNLL1 binds MRE11 and disrupts the MRE11 dimer to limit DNA end resection. The Shieldin complex is recruited to DSBs hours after DYNLL1, predominantly in G1 cells, and its localization depends on MRE11 activity and is regulated by the DYNLL1-MRE11 interaction. Constitutive association of DYNLL1 with MRE11 can resensitize Shieldin-deficient BRCA1-null cells to PARP inhibitors. Co-immunoprecipitation, DSB localization assays, PARP inhibitor sensitivity, cell-cycle analysis Nature structural & molecular biology High 37696958
2020 Dynll1 forms a persistent complex with mitochondrial cytochrome oxidase Cox4i1 in dendritic cells. Pathogen (Listeria monocytogenes) infection disturbs the Dynll1-Cox4i1 complex; dissociation of this complex is required for release of mitochondrial reactive oxygen species and regulation of intracellular bacterial proliferation. Dynll1 functions as an inhibitor of mitochondrial ROS production. Mass spectrometry, co-immunoprecipitation, ROS measurement, bacterial proliferation assay in dendritic cells Infection and immunity Medium 32041786
2020 LC8 (DYNLL1) binds predominantly in-register to the multivalent IDP domain of ASCIZ (which has three LC8 recognition motifs); at substoichiometric concentrations, one motif is preferentially bound. Linker length between motifs and motif specificity drive the in-register binding mode. NMR chemical shift perturbation, analytical ultracentrifugation, native electrospray ionization mass spectrometry, saturation transfer difference NMR The Journal of biological chemistry Medium 32139510
2021 ASCIZ and DYNLL1 are essential for development and expansion of MYC-driven B cell lymphoma. DYNLL1 levels are co-activated by ASCIZ and MYC. Deletion of Asciz or Dynll1 prevented abnormal pre-B cell expansion in pre-cancerous Eµ-Myc mice, potentiated MYC-induced apoptosis, and delayed lymphoma development; induced deletion of Asciz in established lymphomas extended survival. Genetic deletion (constitutive and inducible) in Eµ-Myc mouse lymphoma model, flow cytometry, apoptosis assays Cell reports High 26832406
2005 DYNLL1 (DNCL1) interacts with the C-terminal domain of PAX6 transcription factor; three PAX6 C-terminal mutations found in patients with eye malformations reduce or abolish the PAX6-DNCL1 interaction, suggesting this interaction may be relevant to PAX6-dependent neurological function. Yeast two-hybrid library screen, mutagenesis of PAX6 patient alleles BMC genetics Low 16098226
2008 In nitrergic varicosities of mouse gut, LC8 (DYNLL1/PIN) is associated with all cytosolic forms of nNOS (320-, 250-, 155-kDa) but is absent from membrane-associated nNOS. All cytosolic nNOS associated with LC8 is catalytically inactive and serine847-phosphorylated. LC8 does not associate with calmodulin-bound (active) nNOS, suggesting LC8 may transport inactive nNOS to the membrane where it dissociates. Co-immunoprecipitation, subcellular fractionation, in vitro nitric oxide assay American journal of physiology. Gastrointestinal and liver physiology Medium 18635601
2010 DYNLL1 directly interacts with two newly characterized targets — African swine fever virus protein p54 and the postsynaptic scaffolding protein gephyrin — through motifs homologous to GIQVD or KXTQT consensus sequences. NMR demonstrates direct interaction and structural modeling shows the overall binding mode is preserved as in other complexes, despite residue-level differences. NMR binding experiments, structural modeling FEBS letters Medium 21094642
2022 DLEU1 lncRNA promotes cell survival in esophageal squamous cell carcinoma by binding and stabilizing DYNLL1 protein, interfering with RNF114-mediated ubiquitination and proteasomal degradation of DYNLL1. The DLEU1/DYNLL1 axis upregulates antiapoptotic BCL2. This identifies RNF114 as an E3 ubiquitin ligase that can target DYNLL1 for proteasomal degradation. RNA pulldown, co-immunoprecipitation, ubiquitination assay, siRNA knockdown, xenograft tumor models Journal of translational medicine Medium 35619131

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2015 PIN-dependent auxin transport: action, regulation, and evolution. The Plant cell 564 25604445
2009 The PIN-FORMED (PIN) protein family of auxin transporters. Genome biology 351 20053306
2005 The PIN auxin efflux facilitators: evolutionary and functional perspectives. Trends in plant science 260 15817418
2018 DYNLL1 binds to MRE11 to limit DNA end resection in BRCA1-deficient cells. Nature 188 30464262
2009 PIN phosphorylation is sufficient to mediate PIN polarity and direct auxin transport. Proceedings of the National Academy of Sciences of the United States of America 162 20080776
2000 Dependence and independence of [PSI(+)] and [PIN(+)]: a two-prion system in yeast? The EMBO journal 161 10790361
2010 The PIN-domain ribonucleases and the prokaryotic VapBC toxin-antitoxin array. Protein engineering, design & selection : PEDS 152 21036780
1999 Structure of the PIN/LC8 dimer with a bound peptide. Nature structural biology 143 10426949
2009 Subcellular trafficking of PIN auxin efflux carriers in auxin transport. European journal of cell biology 136 19944476
2014 Plasma membrane-targeted PIN proteins drive shoot development in a moss. Current biology : CB 121 25448003
2018 Activation and Polarity Control of PIN-FORMED Auxin Transporters by Phosphorylation. Trends in plant science 120 29678589
2006 The plasma membrane recycling pathway and cell polarity in plants: studies on PIN proteins. Journal of cell science 114 16522683
2011 DYNLL/LC8: a light chain subunit of the dynein motor complex and beyond. The FEBS journal 108 21777386
2018 The PIN-FORMED Auxin Efflux Carriers in Plants. International journal of molecular sciences 106 30223430
2020 Naphthylphthalamic acid associates with and inhibits PIN auxin transporters. Proceedings of the National Academy of Sciences of the United States of America 105 33443187
2008 Cellular and molecular requirements for polar PIN targeting and transcytosis in plants. Molecular plant 103 19825603
2005 The PIN-domain toxin-antitoxin array in mycobacteria. Trends in microbiology 101 15993073
2014 D6 PROTEIN KINASE activates auxin transport-dependent growth and PIN-FORMED phosphorylation at the plasma membrane. Developmental cell 99 24930721
2019 PIN-FORMED and PIN-LIKES auxin transport facilitators. Development (Cambridge, England) 90 31371525
2018 The ASCIZ-DYNLL1 axis promotes 53BP1-dependent non-homologous end joining and PARP inhibitor sensitivity. Nature communications 87 30559443
2008 Dynein light chain LC8 negatively regulates NF-kappaB through the redox-dependent interaction with IkappaBalpha. The Journal of biological chemistry 87 18579519
2007 Interactions of PIN and PGP auxin transport mechanisms. Biochemical Society transactions 82 17233620
2017 Comprehensive classification of the PIN domain-like superfamily. Nucleic acids research 80 28575517
2020 Flavonol-mediated stabilization of PIN efflux complexes regulates polar auxin transport. The EMBO journal 75 33185277
2007 Structure and dynamics of LC8 complexes with KXTQT-motif peptides: swallow and dynein intermediate chain compete for a common site. Journal of molecular biology 74 17570393
2003 Destabilizing interactions among [PSI(+)] and [PIN(+)] yeast prion variants. Genetics 73 14704158
2001 Dimerization and folding of LC8, a highly conserved light chain of cytoplasmic dynein. Biochemistry 71 11327818
2020 Receptor kinase module targets PIN-dependent auxin transport during canalization. Science (New York, N.Y.) 66 33122378
2009 Dynein light chain LC8 regulates syntaphilin-mediated mitochondrial docking in axons. The Journal of neuroscience : the official journal of the Society for Neuroscience 65 19641106
2021 PIN-mediated polar auxin transport regulations in plant tropic responses. The New phytologist 63 34254313
2017 Reassessing the Roles of PIN Proteins and Anticlinal Microtubules during Pavement Cell Morphogenesis. Plant physiology 62 29192026
2020 Strigolactones inhibit auxin feedback on PIN-dependent auxin transport canalization. Nature communications 60 32665554
2019 The Nuts and Bolts of PIN Auxin Efflux Carriers. Frontiers in plant science 57 31417597
1992 Prostatic intraepithelial neoplasia (PIN): current concepts. Journal of cellular biochemistry. Supplement 57 1289664
2011 ATM substrate Chk2-interacting Zn2+ finger (ASCIZ) Is a bi-functional transcriptional activator and feedback sensor in the regulation of dynein light chain (DYNLL1) expression. The Journal of biological chemistry 55 22167198
2014 Intracellular trafficking and PIN-mediated cell polarity during tropic responses in plants. Current opinion in plant biology 52 25553419
1998 Mitogen-activated protein kinases and apoptosis in PIN. Virchows Archiv : an international journal of pathology 51 9645439
2015 The PIN domain of EXO1 recognizes poly(ADP-ribose) in DNA damage response. Nucleic acids research 49 26400172
2015 Ebola virus VP35 interaction with dynein LC8 regulates viral RNA synthesis. Journal of virology 47 25741013
2012 Posttranslational modification and trafficking of PIN auxin efflux carriers. Mechanisms of development 46 22425600
2017 Structural conservation of the PIN domain active site across all domains of life. Protein science : a publication of the Protein Society 45 28508407
2008 Biochemical and structural characterization of the Pak1-LC8 interaction. The Journal of biological chemistry 44 18650427
2009 Interaction with LC8 is required for Pak1 nuclear import and is indispensable for zebrafish development. PloS one 42 19557173
2021 AGC kinases and MAB4/MEL proteins maintain PIN polarity by limiting lateral diffusion in plant cells. Current biology : CB 40 33705718
2021 Phosphorylation control of PIN auxin transporters. Current opinion in plant biology 39 34974229
2019 LC8/DYNLL1 is a 53BP1 effector and regulates checkpoint activation. Nucleic acids research 39 30982887
2023 Effect of atmospheric pin-to-plate cold plasma on oat protein: Structural, chemical, and foaming characteristics. International journal of biological macromolecules 38 37257535
2021 Dimerisation of the PICTS complex via LC8/Cut-up drives co-transcriptional transposon silencing in Drosophila. eLife 36 33538693
2012 The Zinc-finger protein ASCIZ regulates B cell development via DYNLL1 and Bim. The Journal of experimental medicine 35 22891272
2022 Systems approaches reveal that ABCB and PIN proteins mediate co-dependent auxin efflux. The Plant cell 34 35302640
2021 Recent developments in the understanding of PIN polarity. The New phytologist 34 34882802
2005 pH driven conformational dynamics and dimer-to-monomer transition in DLC8. Protein science : a publication of the Protein Society 34 16385004
2019 Systematic identification of recognition motifs for the hub protein LC8. Life science alliance 32 31266884
2015 Multivalent IDP assemblies: Unique properties of LC8-associated, IDP duplex scaffolds. FEBS letters 32 26226419
2011 LC8 dynein light chain (DYNLL1) binds to the C-terminal domain of ATM-interacting protein (ATMIN/ASCIZ) and regulates its subcellular localization. Biochemical and biophysical research communications 31 21971545
2008 Differences in dynamic structure of LC8 monomer, dimer, and dimer-peptide complexes. Biochemistry 30 18942858
2007 Identification and characterization of pin and thrum alleles of two genes that co-segregate with the Primula S locus. The Plant journal : for cell and molecular biology 30 17561923
2015 The Anchored Flexibility Model in LC8 Motif Recognition: Insights from the Chica Complex. Biochemistry 29 26652654
2016 The Transcription Factor ASCIZ and Its Target DYNLL1 Are Essential for the Development and Expansion of MYC-Driven B Cell Lymphoma. Cell reports 28 26832406
2023 SHORT ROOT and INDETERMINATE DOMAIN family members govern PIN-FORMED expression to regulate minor vein differentiation in rice. The Plant cell 27 37154077
2024 LYCHOS is a human hybrid of a plant-like PIN transporter and a GPCR. Nature 26 39358511
2024 Over 25 years of decrypting PIN-mediated plant development. Nature communications 26 39548100
2023 Dynamics of the DYNLL1-MRE11 complex regulate DNA end resection and recruitment of Shieldin to DSBs. Nature structural & molecular biology 26 37696958
2020 Topological and system-level protein interaction network (PIN) analyses to deduce molecular mechanism of curcumin. Scientific reports 26 32694520
2019 The LC8-RavP ensemble Structure Evinces A Role for LC8 in Regulating Lyssavirus Polymerase Functionality. Journal of molecular biology 26 31634467
2014 The mechanism of dynein light chain LC8-mediated oligomerization of the Ana2 centriole duplication factor. The Journal of biological chemistry 25 24920673
2012 Dynein light chain 1 (LC8) association enhances microtubule stability and promotes microtubule bundling. The Journal of biological chemistry 25 23038268
2013 Structural analysis of the regulation of the DYNLL/LC8 binding to Nek9 by phosphorylation. The Journal of biological chemistry 24 23482567
2011 DYNLL/LC8 protein controls signal transduction through the Nek9/Nek6 signaling module by regulating Nek6 binding to Nek9. The Journal of biological chemistry 23 21454704
2021 OGT Protein Interaction Network (OGT-PIN): A Curated Database of Experimentally Identified Interaction Proteins of OGT. International journal of molecular sciences 22 34502531
2019 Enhanced Delivery of Plasmid DNA to Skeletal Muscle Cells using a DLC8-Binding Peptide and ASSLNIA-Modified PAMAM Dendrimer. Molecular pharmaceutics 22 30951315
2018 High-affinity heterotetramer formation between the large myelin-associated glycoprotein and the dynein light chain DYNLL1. Journal of neurochemistry 22 30261098
2006 Equilibrium unfolding of DLC8 monomer by urea and guanidine hydrochloride: Distinctive global and residue level features. Biochimie 22 17029744
2022 Waveguide-Integrated MoTe2 p-i-n Homojunction Photodetector. ACS nano 21 36413764
2020 The dynein light chain 8 (LC8) binds predominantly "in-register" to a multivalent intrinsically disordered partner. The Journal of biological chemistry 21 32139510
2023 Antigravitropic PIN polarization maintains non-vertical growth in lateral roots. Nature plants 20 37666965
2020 DYNLL1 is hypomethylated and upregulated in a tumor stage- and grade-dependent manner and associated with increased mortality in hepatocellular carcinoma. Experimental and molecular pathology 20 33171156
2021 PIN and CCCH Zn-finger domains coordinate RNA targeting in ZC3H12 family endoribonucleases. Nucleic acids research 19 33950203
2019 Pinstatic Acid Promotes Auxin Transport by Inhibiting PIN Internalization. Plant physiology 19 30936248
2016 Expression Analysis of PIN Genes in Root Tips and Nodules of Medicago truncatula. International journal of molecular sciences 19 27463709
2012 Development of a recombinant fusion protein based on the dynein light chain LC8 for non-viral gene delivery. Journal of controlled release : official journal of the Controlled Release Society 19 22286006
2010 Structural models of DYNLL1 with interacting partners: African swine fever virus protein p54 and postsynaptic scaffolding protein gephyrin. FEBS letters 19 21094642
2023 PIN-FORMED is required for shoot phototropism/gravitropism and facilitates meristem formation in Marchantia polymorpha. The New phytologist 18 36880411
2023 Substrate recognition and transport mechanism of the PIN-FORMED auxin exporters. Trends in biochemical sciences 18 37574372
2020 Effects of PIN on Osteoblast Differentiation and Matrix Mineralization through Runt-Related Transcription Factor. International journal of molecular sciences 18 33339165
2005 A screen for proteins that interact with PAX6: C-terminal mutations disrupt interaction with HOMER3, DNCL1 and TRIM11. BMC genetics 18 16098226
2024 CALMODULIN-LIKE16 and PIN-LIKES7a cooperatively regulate rice seedling primary root elongation under chilling. Plant physiology 17 38445796
2013 Dynein light chain LC8 inhibits osteoclast differentiation and prevents bone loss in mice. Journal of immunology (Baltimore, Md. : 1950) 17 23293355
2008 NMR comparison of the native energy landscapes of DLC8 dimer and monomer. Biophysical chemistry 17 18241976
2008 PIN/LC8 is associated with cytosolic but not membrane-bound nNOS in the nitrergic varicosities of mice gut: implications for nitrergic neurotransmission. American journal of physiology. Gastrointestinal and liver physiology 17 18635601
2007 Evaluation of an LC8-binding peptide for the attachment of artificial cargo to dynein. Molecular pharmaceutics 17 17274669
2020 The Dynll1-Cox4i1 Complex Regulates Intracellular Pathogen Clearance via Release of Mitochondrial Reactive Oxygen Species. Infection and immunity 16 32041786
2011 Conformational dynamics promote binding diversity of dynein light chain LC8. Biophysical chemistry 16 21621319
2019 Involvement of PIN-like domain nucleases in tRNA processing and translation regulation. IUBMB life 15 31066520
2014 NMR Characterization of Self-Association Domains Promoted by Interactions with LC8 Hub Protein. Computational and structural biotechnology journal 15 24757501
2023 Quantifying cooperative multisite binding in the hub protein LC8 through Bayesian inference. PLoS computational biology 14 37083599
2023 Divergence of trafficking and polarization mechanisms for PIN auxin transporters during land plant evolution. Plant communications 13 37528584
2022 DLEU1 promotes cell survival by preventing DYNLL1 degradation in esophageal squamous cell carcinoma. Journal of translational medicine 13 35619131
2020 In silico analysis of DYNLL1 expression in ovarian cancer chemoresistance. Cell biology international 13 32208526
2014 Arl3 and LC8 regulate dissociation of dynactin from dynein. Nature communications 13 25342295

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