Affinage

Showing PAFAH1B1 — LIS1 is a alias.

PAFAH1B1

Platelet-activating factor acetylhydrolase IB subunit beta · UniProt P43034

Length
410 aa
Mass
46.6 kDa
Annotated
2026-06-10
100 papers in source corpus 35 papers cited in narrative 35 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

PAFAH1B1 (LIS1) is a dosage-sensitive regulator of cytoplasmic dynein that controls nuclear migration, mitotic spindle behavior, and neuronal migration during brain development (PMID:9697693, PMID:16144905, PMID:24030547). It functions as an obligate homodimer formed through its N-terminal coiled-coil, with dimerization required for activity and for regulating the platelet-activating factor acetylhydrolase complex in which LIS1 is a subunit (PMID:11134054, PMID:11344260). LIS1 acts directly on the dynein motor: structural studies show it serves as a molecular wedge between two dynein motor domains to relieve autoinhibition, while microtubule binding induces allosteric conformational changes in dynein that lower LIS1 affinity and permit dissociation, and LIS1 additionally tethers dynactin's p150 subunit during complex assembly (PMID:37620585, PMID:37322240, PMID:38547289). This regulation operates through a conserved LIS1–NudE/NDEL1–dynein axis established by genetic epistasis and direct binding in Aspergillus and mammalian systems, governing nuclear/spindle-pole positioning, microtubule dynamics, and plus-end localization (PMID:9236777, PMID:10931877, PMID:11163258, PMID:11369237, PMID:24030547). At the cellular level LIS1 directs interkinetic nuclear oscillations, somal translocation, and the multipolar-to-bipolar transition in migrating neurons (PMID:16144905), controls spindle orientation and asymmetric inheritance of fate determinants in stem cells (PMID:24030547, PMID:24487275), and remains essential postdevelopmentally for axonal transport in adult neurons (PMID:29404402). LIS1 also interacts with doublecortin, MAP1B, and PDE4 to modulate microtubule binding and dynein engagement, and its stability is maintained through NudCL2-assisted Hsp90 chaperoning (PMID:11001923, PMID:15762842, PMID:21652625, PMID:20133715). Type-1 lissencephaly arises from LIS1 haploinsufficiency, with disease point mutations reducing the amount of correctly folded protein and mapping to the dynein–LIS1 interface (PMID:10583396, PMID:36692009), and Pafah1b1 heterozygosity produces interneuron migration defects, excitatory/inhibitory imbalance, seizures, and memory deficits (PMID:28811646).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1995 High

    Establishing that the LIS1 ortholog NUDF is required for nuclear migration placed the gene within a conserved dynein-dependent motility pathway, before any biochemical mechanism was known.

    Evidence Genetic cloning, complementation, and multicopy suppression in A. nidulans

    PMID:7612965

    Open questions at the time
    • Did not identify a molecular target of NUDF
    • Relationship to dynein not yet established
    • Mammalian function inferred only from homology
  2. 1997 High

    Suppressor genetics linked NUDF directly to the dynein heavy chain, answering whether LIS1 and dynein act in the same pathway.

    Evidence Extragenic suppressor screen and rescue in A. nidulans

    PMID:9236777

    Open questions at the time
    • Did not distinguish direct binding from indirect pathway membership
    • No biochemical demonstration of contact
  3. 1998 High

    Graded mouse alleles established LIS1 as a dosage-sensitive, cell-autonomous regulator of neuronal migration, explaining the lissencephaly haploinsufficiency phenotype at the developmental level.

    Evidence Targeted mouse mutagenesis producing null, heterozygous, and hypomorphic alleles with histological brain analysis

    PMID:9697693

    Open questions at the time
    • Did not define the molecular activity driving migration
    • Cellular mechanism of migration delay not resolved
  4. 1999 Medium

    Biochemical analysis of disease mutations showed lissencephaly haploinsufficiency results from misfolding that reduces functional LIS1, and identified LIS1 as a microtubule-associated phosphoprotein modified by casein kinase II.

    Evidence In vitro mutagenesis with folding assays; subcellular fractionation and in vitro kinase assays

    PMID:10491172 PMID:10583396

    Open questions at the time
    • Functional consequence of CKII phosphorylation not established
    • CDK7/cyclinH/MAT1 association role undefined
  5. 2000 High

    Identification of NudE/mNudE and DCX as physical partners, plus mapping of homodimerization to the coiled-coil, built the protein-interaction architecture connecting LIS1 to the centrosome and microtubules.

    Evidence Yeast two-hybrid, Co-IP, biochemical oligomeric-state analysis, and microtubule polymerization assays in fungal, mouse, and Xenopus systems

    PMID:10931877 PMID:11001923 PMID:11134054 PMID:11163258

    Open questions at the time
    • How these partners coordinate on the same dynein not yet resolved
    • Order of assembly with dynein undefined
  6. 2001 High

    Direct binding assays and the PAF-AH subunit study tied LIS1 to the dynein heavy chain physically and showed LIS1 dimerization regulates PAF-AH enzymatic activity, linking the two faces of the protein.

    Evidence Pull-down with purified components, yeast two-hybrid, plus targeted exon deletion with PAF-AH enzymatic assay and neuron morphology

    PMID:11344260 PMID:11369237 PMID:11509576

    Open questions at the time
    • Mechanistic link between acetylhydrolase activity and migration unresolved
    • Whether LIS1 alters dynein motor mechanics not yet shown
  7. 2005 High

    Live imaging in embryonic brain dissected LIS1's distinct roles in interkinetic nuclear oscillation, the multipolar-to-bipolar transition, and somal translocation, while MAP1B competition revealed a regulatory switch over LIS1-dynein engagement.

    Evidence In utero electroporation with time-lapse slice imaging; Co-IP and competition assays in hippocampal neurons; fungal spindle-pole localization genetics

    PMID:15762842 PMID:15930134 PMID:16144905

    Open questions at the time
    • Molecular trigger for the multipolar-to-bipolar switch unknown
    • How MAP1B phosphorylation is regulated in vivo undefined
  8. 2010 Medium

    NudCL2 was shown to stabilize LIS1 via Hsp90, answering how cellular LIS1 levels are maintained given dosage sensitivity.

    Evidence Co-IP, RNAi, and Hsp90 pharmacological inhibition in mammalian cells

    PMID:20133715

    Open questions at the time
    • Single lab without independent confirmation
    • Quantitative contribution to in vivo LIS1 dosage unmeasured
  9. 2011 Medium

    PDE4 was identified as a competitive LIS1 binder, establishing a cAMP/PKA-regulated mechanism that sequesters LIS1 from dynein to tune transport and migration.

    Evidence Direct binding, Co-IP, microtubule transport and wound-healing migration assays, PKA phosphorylation assay

    PMID:21652625

    Open questions at the time
    • Physiological context where PDE4 competition dominates not defined
    • Single lab
  10. 2014 High

    Conditional knockouts extended LIS1's spindle-orientation role to asymmetric stem cell division and leukemia propagation, broadening its function beyond the developing brain.

    Evidence Conditional KO with real-time imaging of spindle positioning, transplantation, and leukemia propagation assays; mitotic MEF imaging with NDEL1-dynein rescue

    PMID:24030547 PMID:24487275

    Open questions at the time
    • Identity of asymmetrically segregated fate determinants incompletely defined
    • Therapeutic window for leukemia targeting unaddressed
  11. 2017 Medium

    Haploinsufficiency phenotyping connected LIS1 dosage to interneuron migration, excitatory/inhibitory imbalance, seizures, and memory deficits, and the postdevelopmental KO revealed an ongoing requirement for axonal transport.

    Evidence Heterozygous mouse with patch-clamp, EEG, and behavior; tamoxifen-induced adult KO with DRG axonal transport assays

    PMID:28811646 PMID:29404402

    Open questions at the time
    • Adult KO mechanism inferred from cultured DRG neurons
    • Link between transport defect and specific neurological symptoms incomplete
  12. 2024 High

    Cryo-EM structures resolved the long-standing question of how LIS1 regulates dynein mechanochemistry: it wedges between two motor domains to relieve autoinhibition, is allosterically released upon microtubule binding, and tethers dynactin p150, defining LIS1 as an activation factor for processive transport.

    Evidence High-resolution cryo-EM of yeast and human dynein-LIS1, engineered MT-bound/unbound mutants, structure-guided mutagenesis validated in vivo and by in vitro reconstitution

    PMID:34994688 PMID:36692009 PMID:37322240 PMID:37620585 PMID:38547289

    Open questions at the time
    • How NudE/NDEL1 integrates with the wedge mechanism not fully resolved
    • Differences between yeast and human interfaces not exhaustively mapped to function

Open questions

Synthesis pass · forward-looking unresolved questions
  • How LIS1's developmental and dynein-regulatory functions reconcile with non-neuronal roles in angiogenesis, the blood-testis barrier, and PAF-AH catalysis remains unresolved.
  • Whether transcriptional roles at the MGP promoter are dynein-independent unknown
  • Mechanistic basis of PAFAH1B1-IQGAP1 actin regulation in Sertoli cells underexplored
  • Integration of acetylhydrolase activity with dynein function unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008092 cytoskeletal protein binding 4 GO:0098772 molecular function regulator activity 4 GO:0060090 molecular adaptor activity 3
Localization
GO:0005815 microtubule organizing center 3 GO:0005856 cytoskeleton 3 GO:0005829 cytosol 2
Pathway
R-HSA-9609507 Protein localization 4 R-HSA-1266738 Developmental Biology 3 R-HSA-1640170 Cell Cycle 2
Partners
DCTN1DCXDYNC1H1IQGAP1MAP1BNDE1/NDEL1NUDCL2PDE4
Complex memberships
LIS1-NDEL1-dynein complexdynein-dynactin-LIS1 complexplatelet-activating factor acetylhydrolase (PAF-AH 1b)

Evidence

Reading pass · 35 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 Graded reduction of Pafah1b1 (Lis1) activity in mice causes dosage-sensitive neuronal migration defects: homozygous null mice die early post-implantation, heterozygotes show cortical/hippocampal/olfactory bulb disorganization due to delayed neuronal migration via a cell-autonomous neuronal pathway, and further reduction causes more severe brain disorganization including cerebellar defects. Targeted mouse mutagenesis producing three alleles (null, heterozygous, hypomorphic); histological and behavioral analysis of brain lamination and neuronal migration Nature genetics High 9697693
1995 NudF (NUDF), the Aspergillus nidulans ortholog of human LIS1 (42% sequence identity), is required for nuclear migration during vegetative growth and development; NUDF protein level is controlled by NUDC, and extra copies of nudF suppress the nudC3 mutation, placing NUDF in the NUDC pathway for nuclear/dynein-dependent migration. Genetic cloning and complementation in A. nidulans; multicopy suppression assay; sequence homology analysis Molecular biology of the cell High 7612965
2000 LIS1 interacts with mNudE, a mouse homolog of the nuclear distribution gene NUDE; mNudE localizes to the centrosome/MTOC and interacts with six centrosomal proteins. Overexpression of mNudE dissociates gamma-tubulin from the centrosome and disrupts microtubule organization. Missense mutations that disrupt LIS1 function block LIS1-mNudE binding. Misexpression of the LIS1-binding domain of mNudE in Xenopus embryos disrupts CNS lamination. Co-immunoprecipitation; yeast two-hybrid; site-directed mutagenesis; Xenopus misexpression; immunofluorescence/centrosome fractionation Neuron High 11163258
2001 NUDF (LIS1 ortholog) and NUDF's binding partner NUDE directly bind to specific subunits of cytoplasmic dynein: NUDF binds directly to alpha- and gamma-tubulin and to the first P-loop of the dynein heavy chain; NUDE binds directly to alpha- and gamma-tubulin, the dynactin subunit NUDK (Arp1), and the dynein LC8 light chain NUDG. This establishes a direct role for NUDF/LIS1 in regulation of the dynein heavy chain. Direct binding assays (pull-down with purified components); yeast two-hybrid The Journal of biological chemistry High 11509576
2000 NUDF (LIS1 homolog in A. nidulans) is a homodimer in vivo; dimerization occurs via the N-terminal coiled-coil region and is required for NUDF function supporting growth of A. nidulans. Single-step purification of NUDF to homogeneity; biochemical analysis of oligomeric state (gel filtration, sedimentation) The Journal of biological chemistry High 11134054
2000 NUDF (A. nidulans LIS1 homolog) interacts with the coiled-coil domain of NUDE (A. nidulans homolog of mammalian NudE/NUDEL); human LIS1 interacts with the human homologue of NUDE coiled-coil and with Xenopus MP43 coiled-coil. NUDF co-precipitates with epitope-tagged NUDE, and the NH2-terminal coiled-coil domain of NUDE suffices for function when overexpressed. Yeast two-hybrid; co-immunoprecipitation; multicopy suppressor screen The Journal of cell biology High 10931877
2001 LIS1 is a subunit of platelet-activating factor acetylhydrolase (PAF-AH) in vivo; a mutant sLIS1 protein lacking the N-terminal domain cannot dimerize and shows elevated PAF-AH enzymatic activity in embryos, demonstrating that LIS1 dimerization regulates PAF-AH activity in vivo. The mutation also causes aberrant morphology of cortical neurons and radial glia with slower neuronal migration. Targeted deletion of first coding exon; gel filtration for dimerization; PAF-AH enzymatic assay in embryo extracts; live cortical neuron morphology analysis Proceedings of the National Academy of Sciences of the United States of America High 11344260
1997 Suppressor mutations in the nudA gene (cytoplasmic dynein heavy chain) partially suppress the nuclear migration defect of nudF (LIS1 homolog) in A. nidulans, establishing that NUDF and the dynein heavy chain act in the same nuclear migration pathway. Extragenic suppressor screen; genetic complementation mapping; transformation rescue Molecular & general genetics High 9236777
2005 LIS1 RNA interference in embryonic rat brain causes: (1) accumulation of multipolar progenitor cells in the SVZ due to complete failure to transition to bipolar migratory state; (2) abolition of interkinetic nuclear oscillations in radial glial progenitors; (3) block of cell divisions at the ventricular surface; (4) block of somal translocation in bipolar cells in the intermediate zone; (5) cessation of axonal growth—identifying multiple distinct roles for LIS1 in nucleokinesis and process dynamics. In utero electroporation of LIS1 siRNA and dominant-negative constructs; in situ time-lapse imaging of brain slices The Journal of cell biology High 16144905
2000 LIS1 and DCX (doublecortin) physically interact both in vitro and in vivo (co-immunoprecipitation from COS cells and from embryonic brain extracts). The two proteins co-localize in transfected and primary neuronal cells. Both interact with tubulin/microtubules, and together enhance tubulin polymerization additively. In competition assays, DCX can compete with LIS1 for microtubule binding depending on order of addition. Co-immunoprecipitation (overexpressed and endogenous proteins); in vitro microtubule polymerization assay; co-localization by immunofluorescence; domain mapping Human molecular genetics High 11001923
1999 LIS1 is a microtubule-associated phosphoprotein. Phosphorylated LIS1 is enriched in the MAP fraction. LIS1 is phosphorylated on serine residues (alkaline phosphatase-sensitive); a 50-kDa LIS1 kinase is enriched in microtubule-associated fractions; in vitro, LIS1 is phosphorylated by casein kinase II (CKII) but not by several other tested kinases. LIS1 was also found in a complex with CDK7/cyclin H/MAT1 (CAK) and a spleen protein-tyrosine kinase. Subcellular fractionation; phosphoamino acid analysis; in-gel kinase assay; in vitro kinase assay with CKII and other kinases; co-immunoprecipitation European journal of biochemistry Medium 10491172
2001 In A. nidulans, NUDF (LIS1 ortholog) and cytoplasmic dynein heavy chain (NUDA) both localize to microtubule plus-ends as dynamic comet-like structures. Loss-of-function mutations in nudA and nudF reduce microtubule catastrophe frequency, reduce shrinkage rate during catastrophe, and reduce rescue frequency, demonstrating that LIS1/NUDF and dynein regulate microtubule dynamics in vivo. Live-cell GFP imaging of NUDF and NUDA; GFP-tubulin microtubule dynamics analysis in temperature-sensitive nudA and nudF mutants Current biology High 11369237
2013 LIS1 is required for mitotic spindle regulation: LIS1 controls chromosome congression/segregation and kinetochore-microtubule interactions, maintains centrosome number (spindle pole integrity), and regulates spindle orientation by increasing astral MT plus-end movements toward the cell cortex. These functions operate via the LIS1-NDEL1-dynein complex: overexpression of NDEL1-dynein and MT stabilization rescues spindle orientation defects in Lis1 mutants. Time-lapse live-cell imaging of Lis1 mutant mouse embryonic fibroblasts; immunofluorescence; genetic rescue by NDEL1-dynein overexpression and taxol treatment Human molecular genetics High 24030547
2014 LIS1 (Lis1/Pafah1b1) is required for hematopoietic stem cell (HSC) function and leukemogenesis. Conditional hematopoietic deletion of Lis1 causes severe bloodless phenotype, depletion of the stem cell pool, and embryonic lethality. Real-time imaging shows loss of Lis1 causes defects in spindle positioning and asymmetric inheritance of cell fate determinants, triggering accelerated differentiation. Lis1 deletion also blocks myeloid leukemia propagation and improves survival. Conditional knockout (Cre-lox); real-time imaging of spindle positioning and fate determinant segregation; HSC transplantation assays; leukemia propagation assay Nature genetics High 24487275
2010 NudCL2 (NudC-like protein 2) stabilizes LIS1 through Hsp90 chaperone. NudCL2 localizes similarly to LIS1 and dynein (centrosome in interphase; spindle poles and kinetochores in mitosis). Depletion of NudCL2 destabilizes LIS1; NudCL2 complexes with and enhances the LIS1-Hsp90 interaction. Disruption of LIS1-Hsp90 interaction or inhibition of Hsp90 ATPase (geldanamycin) decreases LIS1 stability. Co-immunoprecipitation; RNAi knockdown; pharmacological Hsp90 inhibition; immunofluorescence localization; western blotting Proceedings of the National Academy of Sciences of the United States of America Medium 20133715
2022 High-resolution (3.1 Å) cryo-EM structure of yeast dynein bound to Pac1 (yeast LIS1 homolog) reveals molecular details of dynein-LIS1 contacts and contacts between LIS1's β-propellers. Structure-guided mutations at these contact sites abolish Lis1's ability to regulate yeast dynein mechanochemistry in vivo and to form fully active human dynein complexes in vitro. Cryo-EM structure determination at 3.1 Å; structure-guided mutagenesis; in vitro reconstitution of active human dynein complexes; yeast in vivo functional assays eLife High 34994688
2023 Lis1 relieves dynein autoinhibition by acting as a molecular wedge. Cryo-EM structure of two yeast dynein motor domains with two Lis1 dimers wedged between them ('Chi' conformation) reveals a proposed intermediate in dynein's activation pathway. Contact sites in this structure are required for Lis1 regulation of dynein in S. cerevisiae in vivo and for formation of active human dynein-dynactin-activating adaptor complexes in vitro. Cryo-EM structure determination; structure-guided mutagenesis; yeast in vivo assays; in vitro reconstitution of human dynein-dynactin-adaptor complexes Nature structural & molecular biology High 37620585
2024 Cryo-EM structure of the dynein-dynactin complex on microtubules with LIS1 and the lysosomal adaptor JIP3 reveals that LIS1 unexpectedly binds dynactin's p150 subunit, tethering it along the length of dynein during complex formation. This structure reveals the molecular basis of dynein activation and shows how JIP3 activates dynein despite its atypical architecture. Cryo-EM structure determination of the dynein-dynactin-LIS1-JIP3 complex on microtubules Science High 38547289
2023 Microtubule binding induces conformational changes in dynein that reduce LIS1 affinity (allosteric regulation). Dynein engineered in a microtubule-bound state has low LIS1 affinity; microtubule-unbound state binds LIS1 with high affinity and results in near-irreversible plus-end association. Three cryo-EM structures of human dynein with and without LIS1 reveal microtubule-binding-induced conformational changes responsible. A monomeric motor domain is sufficient for these opposing affinities, and the mechanism is conserved between yeast and humans. Engineered dynein mutants locked in MT-bound or MT-unbound states; cryo-EM structures of human dynein ± LIS1; in vitro binding assays Nature structural & molecular biology High 37322240
2023 Cryo-EM structures of human dynein-LIS1 complexes reveal differences from the yeast system in how dynein and LIS1 interact, provide a blueprint for disrupting human dynein-LIS1 interactions, and map type-1 lissencephaly disease mutations and dynein mutations linked to malformations of cortical development in the context of the dynein-LIS1 interface. Cryo-EM structure determination of human dynein-LIS1 complexes eLife Medium 36692009
2007 Point mutations in the stem region (nudAL1098F) and the fourth AAA domain (nudAR3086C) of dynein heavy chain partially suppress the phenotype of NUDF (LIS1 homolog) deletion in A. nidulans. The nudAR3086C mutation decreases dynein's basal ATPase activity and increases dynein distribution along microtubules, suggesting LIS1/NUDF loss is partially compensated by mechanisms other than enhancement of dynein ATPase activity. Genetic suppressor analysis; ATPase activity assay; immunofluorescence of dynein distribution in mutants Genetics Medium 17237507
1999 Analysis of lissencephaly-causing LIS1 point mutations and internal deletions shows they reduce the amount of correctly folded LIS1 protein (assessed by resistance to trypsin cleavage, gel filtration, and sucrose density gradient centrifugation), indicating that haploinsufficiency in lissencephaly results primarily from folding defects that reduce functional LIS1. In vitro mutagenesis; trypsin sensitivity assay; gel filtration; sucrose density gradient centrifugation European journal of biochemistry Medium 10583396
2005 MAP1B and LIS1 co-localize, associate, and interact physically in hippocampal neurons. The interaction is regulated by MAP1B phosphorylation. This interaction interferes with LIS1-dynein association: MAP1B binding to LIS1 competes with dynein binding, providing a mechanism to regulate the LIS1-dynein complex and neuronal migration/process extension. Co-immunoprecipitation from hippocampal neurons; co-localization by immunofluorescence; competition binding assay The Biochemical journal Medium 15762842
2005 HIV-1 Tat protein interacts with LIS1 both in vitro and in vivo. Tat was identified as a LIS1-interacting protein during biochemical fractionation; Tat interacted with LIS1 but not with CDK7, cyclin H, or MAT1 in vitro; LIS1 co-immunoprecipitated with Tat in HeLa cells; the interaction was confirmed in a yeast two-hybrid system. Biochemical fractionation; in vitro binding assay; co-immunoprecipitation from HeLa cells; yeast two-hybrid Retrovirology Low 15698475
2011 PDE4 (cAMP-specific phosphodiesterase 4) directly binds LIS1. Upregulation of PDE4 sequesters LIS1 away from dynein, impairing dynein-dependent microtubule transport and directed cell migration in wounded monolayer assays. PKA phosphorylation of PDE4 long isoforms within their UCR1 domain selectively augments the PDE4-LIS1 interaction, providing a cAMP/PKA-dependent mechanism to regulate dynein function via LIS1 competition. Direct binding assays; co-immunoprecipitation; microtubule transport assay; wound-healing cell migration assay; PKA phosphorylation assay Journal of cell science Medium 21652625
2006 In A. nidulans, both CLIPA (CLIP-170 homolog) and NUDE independently recruit NUDF (LIS1 homolog) to microtubule plus-ends; deletion of both clipA and nudE nearly completely abolishes NUDF plus-end comets, whereas single deletions have modest effects. CLIPA deletion affects cytoplasmic microtubule dynamics (fewer microtubules undergoing long-range growth, but those reaching the tip are less likely to undergo catastrophe), revealing CLIPA as both a growth-promoting factor and a microtubule dynamics regulator. Gene deletions; GFP live-cell imaging of NUDF, dynein heavy chain, p150-dynactin, and CLIPA; microtubule dynamics analysis Molecular biology of the cell Medium 16467375
2005 In A. nidulans, NUDF (LIS1) localization to spindle poles during mitosis requires a functional NUDF, but does not require a fully functional dynein motor or the anaphase-promoting complex (APC). Conversely, cytoplasmic dynein's spindle pole localization requires APC function and is dependent on NUDF function. A gamma-tubulin mutation (mipAR63) nearly eliminates dynein's spindle pole localization but not NUDF's, indicating NUDF and dynein are targeted to spindle poles by different mechanisms. Genetic epistasis with APC, dynein, NUDF, and gamma-tubulin mutants; immunofluorescence localization; live cell chromosome segregation analysis Molecular biology of the cell Medium 15930134
2003 In A. nidulans, NUDF overproduction totally suppresses deletion of nudE, indicating NUDE function is secondary to that of NUDF. An allele-specific interaction between nudF and nudA (dynein heavy chain) suggests direct interaction between NUDF and dynein heavy chain. NUDF overproduction inhibits certain nudA and apsA (cortical protein) mutants, suggesting a role for NUDF at the cell cortex. Genetic epistasis and overexpression; live-cell GFP imaging of NUDF, NUDA, and NUDE; allele-specific suppressor analysis Molecular biology of the cell Medium 12631710
2008 NUDF (LIS1 homolog) and NUDC directly interact via NUDF's WD40 domain (yeast two-hybrid). NUDC-GFP localizes to spindle pole bodies (SPBs) and bimolecular fluorescence complementation shows NUDC directly interacts with NUDF at SPBs throughout the cell cycle. A new NUDF-associated protein BNFA localizes to SPBs in a NUDF-dependent manner and accumulates in cytoplasm when NUDF is lost. Yeast two-hybrid; bimolecular fluorescence complementation microscopy; tandem affinity purification; GFP live-cell imaging Eukaryotic cell Medium 18390647
2018 Lis1 knockdown in NIH3T3 cells reduces cell migration speed and traction force generation against the extracellular matrix (measured by traction force microscopy). Lis1 KD causes disorganization of microtubules and actin filaments and significantly reduces focal adhesions at the cell periphery. RNAi knockdown; traction force microscopy; live-cell imaging; immunostaining of cytoskeletal components and focal adhesions Biochemical and biophysical research communications Medium 29470990
2017 PAFAH1B1 haploinsufficiency (Pafah1b1+/−) slows tangential migration of GABAergic interneurons into the developing hippocampus, reduces density of parvalbumin- and somatostatin-positive interneurons in dentate gyrus (but not calretinin interneurons), increases excitatory and decreases inhibitory synaptic inputs onto granule cells (measured by whole-cell patch-clamp), and causes spontaneous electrographic seizures and long-term contextual memory deficits. Heterozygous mouse model; immunofluorescence quantification of interneuron subtypes; whole-cell patch-clamp recordings; in vivo EEG; behavioral testing Scientific reports High 28811646
2018 Homozygous Lis1 knockout in adult mice (via tamoxifen-induced Cre) rapidly causes neurological symptoms attributable to Lis1 loss in midbrain/hindbrain (brainstem cardiorespiratory centers show axonal dysfunction). DRG neurons from KO animals show axonal transport defects, neurofilament alterations, and varicosities in culture, implicating defective axonal transport as a mechanism of Lis1's essential postdevelopmental role. Tamoxifen-induced conditional KO; Cre reporter; neurological phenotyping; axonal transport assays in cultured DRG neurons; immunofluorescence of axonal markers eNeuro Medium 29404402
2022 In Sertoli cells, miR-181c/d represses PAFAH1B1 expression, reduces the PAFAH1B1-IQGAP1 complex, and inhibits the CDC42/PAK1/LIMK1/Cofilin pathway required for F-actin stabilization, thereby perturbing blood-testis barrier function and Sertoli cell survival. miRNA mimic overexpression; siRNA knockdown; immunoprecipitation; western blotting; F-actin imaging; in vivo lentiviral injection in mouse testes Cellular and molecular life sciences Medium 36008729
2016 PAFAH1B1 is required for endothelial angiogenic function: knockdown impairs tube formation and sprouting in HUVECs; overexpression increases tube number and sprout length. PAFAH1B1 maintains Matrix Gla Protein (MGP) expression and is required for active histone marks and proper binding of RNA Polymerase II to the MGP transcriptional start site (chromatin immunoprecipitation). MGP is itself required for endothelial angiogenic capacity. RNAi knockdown; overexpression; tube formation and spheroid sprouting assays; microarray; chromatin immunoprecipitation (ChIP) Acta physiologica Medium 27124368
2008 Pafah1b2 (Alpha2) mutations suppress the hydrocephalus phenotype of Pafah1b1;Reln and Pafah1b1;Dab1 compound mutant mice, while Pafah1b3 (Alpha1) mutations exacerbate layering defects. This genetic epistasis reveals that the two Pafah1b alpha subunits have profoundly different effects on brain development and interact differently with the Reelin signaling pathway. Triple mouse mutant generation; genetic epistasis; histological analysis of cortical layering and hydrocephalus Neuroscience letters Medium 18514414

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1998 Graded reduction of Pafah1b1 (Lis1) activity results in neuronal migration defects and early embryonic lethality. Nature genetics 481 9697693
1993 Lissencephaly. A human brain malformation associated with deletion of the LIS1 gene located at chromosome 17p13. JAMA 324 7907669
2005 LIS1 RNA interference blocks neural stem cell division, morphogenesis, and motility at multiple stages. The Journal of cell biology 314 16144905
2019 Genetics of MDS. Blood 310 30670442
1995 NudF, a nuclear migration gene in Aspergillus nidulans, is similar to the human LIS-1 gene required for neuronal migration. Molecular biology of the cell 292 7612965
2000 LIS1 regulates CNS lamination by interacting with mNudE, a central component of the centrosome. Neuron 245 11163258
2018 Chronic immune response dysregulation in MDS pathogenesis. Blood 192 30104218
2019 Treatment of MDS. Blood 190 30670446
2009 Increased LIS1 expression affects human and mouse brain development. Nature genetics 185 19136950
2001 The Aspergillus cytoplasmic dynein heavy chain and NUDF localize to microtubule ends and affect microtubule dynamics. Current biology : CB 153 11369237
2020 Genetics of progression from MDS to secondary leukemia. Blood 146 32430504
2000 The LIS1-related NUDF protein of Aspergillus nidulans interacts with the coiled-coil domain of the NUDE/RO11 protein. The Journal of cell biology 146 10931877
2007 Lissencephaly and LIS1: insights into the molecular mechanisms of neuronal migration and development. Clinical genetics 138 17850624
2001 Targeted mutagenesis of Lis1 disrupts cortical development and LIS1 homodimerization. Proceedings of the National Academy of Sciences of the United States of America 132 11344260
2022 Distinguishing AML from MDS: a fixed blast percentage may no longer be optimal. Blood 123 34111285
2000 Interaction between LIS1 and doublecortin, two lissencephaly gene products. Human molecular genetics 116 11001923
1993 Mutations of the p53 gene in myelodysplastic syndrome (MDS) and MDS-derived leukemia. Blood 113 8499637
1995 Lissencephaly gene (LIS1) expression in the CNS suggests a role in neuronal migration. The Journal of neuroscience : the official journal of the Society for Neuroscience 104 7751941
2016 Unraveling the Pathogenesis of MDS: The NLRP3 Inflammasome and Pyroptosis Drive the MDS Phenotype. Frontiers in oncology 95 27379212
2002 Clinical and molecular basis of classical lissencephaly: Mutations in the LIS1 gene (PAFAH1B1). Human mutation 91 11754098
2014 Lis1 regulates asymmetric division in hematopoietic stem cells and in leukemia. Nature genetics 87 24487275
2011 Role of immune responses in the pathogenesis of low-risk MDS and high-risk MDS: implications for immunotherapy. British journal of haematology 82 21488861
1999 Impaired learning and motor behavior in heterozygous Pafah1b1 (Lis1) mutant mice. Learning & memory (Cold Spring Harbor, N.Y.) 82 10541472
2019 Genetic abnormalities and pathophysiology of MDS. International journal of clinical oncology 80 31093808
2016 Mutations of myelodysplastic syndromes (MDS): An update. Mutation research. Reviews in mutation research 80 27543316
2013 LIS1 controls mitosis and mitotic spindle organization via the LIS1-NDEL1-dynein complex. Human molecular genetics 76 24030547
2013 LIS1 functions in normal development and disease. Current opinion in neurobiology 74 23973156
2001 LIS1: cellular function of a disease-causing gene. Trends in cell biology 73 11306294
1997 Mutations in the heavy chain of cytoplasmic dynein suppress the nudF nuclear migration mutation of Aspergillus nidulans. Molecular & general genetics : MGG 72 9236777
2020 Recurrent SRSF2 mutations in MDS affect both splicing and NMD. Genes & development 67 32001512
2018 How I treat MDS after hypomethylating agent failure. Blood 67 30545832
1994 Mutations in LIS1 (ERG6) gene confer increased sodium and lithium uptake in Saccharomyces cerevisiae. Biochimica et biophysica acta 66 8038180
2013 Epigenetic therapies in MDS and AML. Advances in experimental medicine and biology 54 22956506
1999 LIS1 is a microtubule-associated phosphoprotein. European journal of biochemistry 54 10491172
2024 Molecular mechanism of dynein-dynactin complex assembly by LIS1. Science (New York, N.Y.) 53 38547289
2020 Therapy for lower-risk MDS. Hematology. American Society of Hematology. Education Program 50 33275714
2003 Roles of NUDE and NUDF proteins of Aspergillus nidulans: insights from intracellular localization and overexpression effects. Molecular biology of the cell 50 12631710
2009 Many are called MDS cell lines: one is chosen. Leukemia research 47 19344951
2006 CLIP-170 homologue and NUDE play overlapping roles in NUDF localization in Aspergillus nidulans. Molecular biology of the cell 47 16467375
2001 Targeting hypomethylation of DNA to achieve cellular differentiation in myelodysplastic syndromes (MDS). The oncologist 43 11700387
2013 Allogeneic transplantation for AML and MDS: GVL versus GVHD and disease recurrence. Hematology. American Society of Hematology. Education Program 42 24319163
2000 Classical lissencephaly and double cortex (subcortical band heterotopia): LIS1 and doublecortin. Current opinion in neurology 40 10987567
2022 VEXAS Syndrome: A Novelty in MDS Landscape. Diagnostics (Basel, Switzerland) 39 35885496
2018 Current status and trends in the diagnostics of AML and MDS. Blood reviews 38 29728319
2013 Deletion 5q MDS: molecular and therapeutic implications. Best practice & research. Clinical haematology 38 24507813
2005 Molecular Pathogenesis of MDS. Hematology. American Society of Hematology. Education Program 38 16304374
2022 Structural basis for cytoplasmic dynein-1 regulation by Lis1. eLife 37 34994688
2010 Controversies surrounding iron chelation therapy for MDS. Blood reviews 37 21030120
2016 Loss of p300 accelerates MDS-associated leukemogenesis. Leukemia 34 27881875
2001 The LIS1-related protein NUDF of Aspergillus nidulans and its interaction partner NUDE bind directly to specific subunits of dynein and dynactin and to alpha- and gamma-tubulin. The Journal of biological chemistry 34 11509576
2010 Hematopoietic stem cell transplantation for MDS. Hematology/oncology clinics of North America 33 20359634
2007 Location and type of mutation in the LIS1 gene do not predict phenotypic severity. Neurology 33 17664403
2020 Controversies on the Consequences of Iron Overload and Chelation in MDS. HemaSphere 31 32647792
2010 NudC-like protein 2 regulates the LIS1/dynein pathway by stabilizing LIS1 with Hsp90. Proceedings of the National Academy of Sciences of the United States of America 31 20133715
2013 Morphology, cytogenetics and classification of MDS. Best practice & research. Clinical haematology 29 24507811
2005 HIV-1 Tat interacts with LIS1 protein. Retrovirology 29 15698475
2005 Binding of microtubule-associated protein 1B to LIS1 affects the interaction between dynein and LIS1. The Biochemical journal 29 15762842
1999 Analysis of lissencephaly-causing LIS1 mutations. European journal of biochemistry 29 10583396
2021 Risk-Adapted, Individualized Treatment Strategies of Myelodysplastic Syndromes (MDS) and Chronic Myelomonocytic Leukemia (CMML). Cancers 28 33807279
2000 Nudf, a fungal homolog of the human LIS1 protein, functions as a dimer in vivo. The Journal of biological chemistry 28 11134054
2017 Gene fusions PAFAH1B1-USP6 and RUNX2-USP6 in aneurysmal bone cysts identified by next generation sequencing. Cancer genetics 27 28449806
2018 Lis1 dysfunction leads to traction force reduction and cytoskeletal disorganization during cell migration. Biochemical and biophysical research communications 26 29470990
1990 Human chromosome 17 NotI linking clones and their use in long-range restriction mapping of the Miller-Dieker chromosome region (MDCR) in 17p13.3. Genomics 26 2347590
2023 Lis1 relieves cytoplasmic dynein-1 autoinhibition by acting as a molecular wedge. Nature structural & molecular biology 25 37620585
2016 PAFAH1B1 and the lncRNA NONHSAT073641 maintain an angiogenic phenotype in human endothelial cells. Acta physiologica (Oxford, England) 25 27124368
2023 Structures of human dynein in complex with the lissencephaly 1 protein, LIS1. eLife 24 36692009
2022 Transplant for TP53-mutated MDS and AML: because we can or because we should? Hematology. American Society of Hematology. Education Program 24 36485102
2016 Recent advances in the treatment of lower-risk non-del(5q) myelodysplastic syndromes (MDS). Leukemia research 24 27883945
2007 Point mutations in the stem region and the fourth AAA domain of cytoplasmic dynein heavy chain partially suppress the phenotype of NUDF/LIS1 loss in Aspergillus nidulans. Genetics 24 17237507
2012 Epigenetic aspects of MDS and its molecular targeted therapy. International journal of hematology 23 23054654
2020 Targeting the Microenvironment in MDS: The Final Frontier. Frontiers in pharmacology 22 32742264
2014 PP2A: The Achilles Heal in MDS with 5q Deletion. Frontiers in oncology 22 25295231
2010 Genetic deletions in AML and MDS. Best practice & research. Clinical haematology 22 21130407
2005 Cytoplasmic dynein's mitotic spindle pole localization requires a functional anaphase-promoting complex, gamma-tubulin, and NUDF/LIS1 in Aspergillus nidulans. Molecular biology of the cell 21 15930134
2021 Responsible Genes for Neuronal Migration in the Chromosome 17p13.3: Beyond Pafah1b1(Lis1), Crk and Ywhae(14-3-3ε). Brain sciences 20 35053800
2002 LIS1-no more no less. Molecular psychiatry 20 11803439
2023 Microtubule-binding-induced allostery triggers LIS1 dissociation from dynein prior to cargo transport. Nature structural & molecular biology 19 37322240
2022 Recurrent transcriptional responses in AML and MDS patients treated with decitabine. Experimental hematology 19 35429619
2022 The Coming of Age of Preclinical Models of MDS. Frontiers in oncology 18 35372085
2022 Sertoli cell survival and barrier function are regulated by miR-181c/d-Pafah1b1 axis during mammalian spermatogenesis. Cellular and molecular life sciences : CMLS 18 36008729
2022 Cause of death and excess mortality in patients with lower-risk myelodysplastic syndromes (MDS): A report from the European MDS registry. British journal of haematology 18 36335984
2016 Genetic Aspects of Myoclonus-Dystonia Syndrome (MDS). Molecular neurobiology 18 26790671
2008 The nuclear migration protein NUDF/LIS1 forms a complex with NUDC and BNFA at spindle pole bodies. Eukaryotic cell 18 18390647
2008 The role of JAK2 mutations in RARS and other MDS. Hematology. American Society of Hematology. Education Program 18 19074058
2024 p53 biology and reactivation for improved therapy in MDS and AML. Biomarker research 17 38481290
2021 Biology and clinical management of hypoplastic MDS: MDS as a bone marrow failure syndrome. Best practice & research. Clinical haematology 17 34404534
2020 NudCL2 regulates cell migration by stabilizing both myosin-9 and LIS1 with Hsp90. Cell death & disease 17 32665550
2017 PAFAH1B1 haploinsufficiency disrupts GABA neurons and synaptic E/I balance in the dentate gyrus. Scientific reports 17 28811646
2011 Interaction between LIS1 and PDE4, and its role in cytoplasmic dynein function. Journal of cell science 17 21652625
2024 How I reduce and treat posttransplant relapse of MDS. Blood 16 38306658
2021 Germline mutations in MDS/AML predisposition disorders. Current opinion in hematology 16 33394724
2021 Human cytomegalovirus infection is associated with increased expression of the lissencephaly gene PAFAH1B1 encoding LIS1 in neural stem cells and congenitally infected brains. The Journal of pathology 16 33565082
2015 Role of PAFAH1B1 in human spermatogenesis, fertilization and early embryonic development. Reproductive biomedicine online 16 26380866
2022 Targeting inflammation in lower-risk MDS. Hematology. American Society of Hematology. Education Program 15 36485128
2012 Implication of microRNAs in the pathogenesis of MDS. Current pharmaceutical design 14 22571695
2008 Pafah1b2 mutations suppress the development of hydrocephalus in compound Pafah1b1; Reln and Pafah1b1; Dab1 mutant mice. Neuroscience letters 14 18514414
2018 An Essential Postdevelopmental Role for Lis1 in Mice. eNeuro 13 29404402
2016 N-Acetyl-D-Glucosamine Kinase Interacts with Dynein-Lis1-NudE1 Complex and Regulates Cell Division. Molecules and cells 13 27646688
1996 Immunophenotyping of AML and MDS and detection of residual disease. Bailliere's clinical haematology 13 8730550
2019 In MDS, is higher risk higher reward? Hematology. American Society of Hematology. Education Program 12 31808894

Missed literature

Know a paper Affinage missed for PAFAH1B1? Flag it for the maintainers and the community.

No submissions yet.