| 2003 |
Separate regions of HCF-1 critical for cell proliferation associate with the Sin3 histone deacetylase (HDAC) complex and a human trithorax-related Set1/Ash2 histone H3-K4 methyltransferase (HMT) complex; HCF-1 tethers these two complexes together, and the transcriptional activator VP16 selectively binds HCF-1 associated with the Set1/Ash2 HMT complex in the absence of the Sin3 HDAC complex. |
Co-immunoprecipitation, mass spectrometry, in vitro binding assays, domain mapping |
Genes & development |
High |
12670868
|
| 2001 |
HCF-1 is naturally bound to chromatin in uninfected cells through its VP16 interaction domain (Kelch/beta-propeller domain); dissociation from chromatin in tsBN67 cells precedes and causes temperature-induced cell proliferation arrest. |
Chromatin fractionation, temperature-shift experiments, tsBN67 cell proliferation assays |
Molecular and cellular biology |
High |
11340173
|
| 2011 |
O-GlcNAc transferase (OGT) both O-GlcNAcylates the HCF-1N subunit and directly cleaves HCF-1 at the HCF-1PRO repeat sequences, performing site-specific proteolytic maturation; replacement of HCF-1PRO repeats with a heterologous cleavage signal promotes proteolysis but fails to activate HCF-1C M-phase functions, showing that OGT-mediated cleavage is specifically required for HCF-1C function. |
In vitro OGT cleavage assays, mutagenesis of HCF-1PRO repeats, cell-based M-phase progression assays |
Cell |
High |
21295698
|
| 2013 |
The tetratricopeptide-repeat (TPR) domain of OGT binds the C-terminal portion of an HCF-1 proteolytic repeat, positioning the cleavage region in the glycosyltransferase active site above UDP-GlcNAc; cleavage occurs between cysteine and glutamate residues producing a pyroglutamate product; mutation of the cleavage-site glutamate to serine converts an HCF-1 proteolytic repeat into a glycosylation substrate. |
Crystal structure of OGT:HCF-1PRO-repeat complex, active-site mutagenesis, biochemical cleavage assays |
Science |
High |
24311690
|
| 2003 |
HCF-1 regulates two distinct stages of the cell cycle via its two proteolytically generated subunits: HCF-1N promotes G1-phase progression, while HCF-1C ensures proper cytokinesis/exit from mitosis; siRNA depletion of HCF-1 in diverse mammalian cells caused both G1 arrest and cytokinesis defects, and proteolytic processing is required to separate and ensure these functions. |
siRNA knockdown in multiple mammalian cell lines, cell-cycle analysis, cytokinesis assays, expression of separated subunits |
The EMBO journal |
High |
12743030
|
| 2004 |
Depletion of the HCF-1C subunit causes mitotic defects including a switch from monomethyl to dimethyl H4-K20 and defective chromosome alignment/segregation; HCF-1C regulates expression of the H4-K20 methyltransferase PR-Set7, and upregulation of PR-Set7 upon HCF-1 loss leads to improper mitotic H4-K20 methylation and cytokinesis defects. |
siRNA depletion, Western blot for histone modifications, immunofluorescence, PR-Set7 overexpression rescue experiments |
Molecular cell |
High |
15200950
|
| 2007 |
During the G1-to-S phase transition, HCF-1 associates with both activator E2F1/E2F3a and repressor E2F4 proteins; when bound to E2F1, HCF-1 acts as a coactivator and recruits MLL and Set-1 histone H3K4 methyltransferases to E2F-responsive promoters, inducing histone methylation and transcriptional activation. |
Co-immunoprecipitation, chromatin immunoprecipitation (ChIP), cell-cycle-staged cell fractionation, reporter assays |
Molecular cell |
High |
17612494
|
| 2009 |
BAP1 deubiquitinase interacts with HCF-1N via an HCF-1 binding motif (HBM); BAP1 deubiquitinates Lys-48-linked polyubiquitin chains on the Kelch domain of HCF-1N; the HBM of BAP1 is required for both the HCF-1 interaction and BAP1-mediated growth regulation, and dominant-negative BAP1-mediated growth suppression is entirely dependent on the HBM. |
Mass spectrometry of co-purified proteins, co-immunoprecipitation, RNAi depletion, ubiquitin assays, HBM point mutants |
The Journal of biological chemistry |
High |
19815555
|
| 2000 |
HCF-1 contains two matched pairs of self-association sequences (SAS1 and SAS2) mediating HCF-1N:HCF-1C subunit association; SAS1 consists of a 43-aa HCF-1N region that associates with a tandem pair of fibronectin type 3 (Fn3) repeats in HCF-1C; HCF-1C subunits recruit HCF-1N subunits to the nucleus via a C-terminal nuclear localization signal. |
Domain deletion analysis, co-immunoprecipitation, nuclear localization assays |
Molecular and cellular biology |
High |
10958670
|
| 2012 |
Crystal structure of the HCF-1 self-association sequence 1 (SAS1) reveals an interdigitated fibronectin type 3 (Fn3) tandem repeat structure formed by SAS1 elements from HCF-1N and HCF-1C; the C-terminal nuclear localization signal (NLS) recruited by this structure is required for formation of the VP16-induced transcriptional regulatory complex. |
X-ray crystallography, mutagenesis of NLS, VP16-induced complex formation assays |
Proceedings of the National Academy of Sciences |
High |
23045687
|
| 2008 |
C. elegans HCF-1 physically associates with the DAF-16/FOXO transcription factor; loss of hcf-1 causes daf-16-dependent lifespan extension and heightened stress resistance; HCF-1 limits DAF-16 recruitment to target gene promoters and thereby represses a subset of DAF-16-regulated genes. |
Co-immunoprecipitation, ChIP, genetic epistasis (daf-16 mutant suppression), lifespan assays, gene expression profiling |
PLoS biology |
High |
18828672
|
| 2011 |
C. elegans HCF-1 acts downstream of SIR-2.1 in lifespan regulation; SIR-2.1/SIRT1 and HCF-1 form protein complexes in both worms and mammalian cells; 80% overlap in DAF-16 target genes regulated by hcf-1 mutation and sir-2.1 overexpression; mammalian HCF-1 also represses FOXO/SIRT1 target genes, demonstrating conservation of this regulatory axis. |
Co-immunoprecipitation, genetic epistasis analysis, gene expression profiling, lifespan assays |
PLoS genetics |
High |
21909281
|
| 2010 |
THAP1 binds HCF-1 in vitro and associates with HCF-1 and OGT in vivo via a consensus HCF-1 binding motif (HBM); endogenous THAP1 mediates recruitment of HCF-1 to the RRM1 promoter during endothelial cell proliferation; HCF-1 is essential for transcriptional activation of RRM1. |
Proteomic analysis, in vitro binding, co-immunoprecipitation, ChIP, RNAi knockdown, reporter assays |
The Journal of biological chemistry |
High |
20200153
|
| 2010 |
THAP11 (Ronin) binds with HCF-1 to a hyperconserved enhancer element at promoters of genes involved in transcription initiation, mRNA splicing, and cell metabolism in embryonic stem cells; Ronin/HCF-1 binding leads to both repression and activation of target genes essential for protein biosynthesis and energy production. |
ChIP-seq, co-immunoprecipitation, RNAi knockdown, gene expression profiling |
Genes & development |
High |
20581084
|
| 2013 |
In HeLa cells, HCFC1 is bound to ~5,400 active CpG-island promoters; ZNF143, THAP11, YY1, and GABP transcription factors co-localize with HCFC1 at ~90% of HCFC1-bound promoters, revealing that a small set of sequence-specific factors directs HCFC1 to active promoters. |
ChIP-seq, motif analysis, co-localization analysis |
Genome research |
Medium |
23539139
|
| 2002 |
The highly conserved C-terminal WYF domain of HCF-1 interacts with the MYND domain of PDCD2; overexpression of PDCD2 suppresses HCF-1 complementation of the tsBN67 temperature-sensitive proliferation defect; expression of interfering domains of either protein enhances complementation, defining PDCD2 as a negative regulator of HCF-1C. |
Co-immunoprecipitation, domain mapping, tsBN67 cell complementation assay |
Oncogene |
Medium |
12149646
|
| 2002 |
HCF-1 is a component of spliceosomal complexes; it interacts with U1 and U5 splicing snRNPs; the tsBN67 HCF-1 missense mutation disrupts interaction with snRNPs at non-permissive temperature, causing inefficient spliceosome assembly and inhibition of splicing; restoration of wild-type HCF-1 rescues splicing. |
Co-immunoprecipitation with snRNPs, in vitro splicing assays in nuclear extracts, tsBN67 temperature-shift experiments, rescue by wild-type HCF-1 expression |
The EMBO journal |
Medium |
12456665
|
| 2002 |
HCF-1 contains an activation domain (HCF-1AD) in its C-terminal subunit required for maximal transactivation by VP16 and cellular LZIP; p300 augments HCF-1AD activity; cells lacking HCF-1AD show reduced HSV immediate-early gene expression and lower viral titers. |
Reporter gene assays, domain deletion/mutagenesis, infection assays, p300 co-expression |
Proceedings of the National Academy of Sciences |
Medium |
12271126
|
| 2002 |
HCF-1 beta-propeller domain binds a new cellular protein HPIP, which contains an HCF-binding motif and a leucine-rich nuclear export sequence; HPIP shuttles between nucleus and cytoplasm in a CRM1-dependent manner; HPIP overexpression leads to accumulation of HCF-1 in the cytoplasm, suggesting HPIP regulates HCF-1 subcellular localization. |
Co-immunoprecipitation, subcellular fractionation, CRM1 inhibition (leptomycin B), overexpression studies |
The Journal of biological chemistry |
Medium |
12235138
|
| 2006 |
The HCF-1 proteolytic processing domain interacts with FHL2 (four-and-a-half LIM domain-2); FHL2 interacts exclusively with the non-processed HCF-1 precursor; FHL2 and HCF-1 co-stimulate transcription of an HCF-1-dependent target gene; thus, site-specific proteolysis of HCF-1 regulates its interaction with FHL2 and modulates coactivator activity. |
Co-immunoprecipitation, reporter gene assay, domain analysis with processed vs. unprocessed HCF-1 |
Proceedings of the National Academy of Sciences |
Medium |
16624878
|
| 2010 |
HCF-1 localizes to the Golgi apparatus in unstimulated sensory neurons; upon Golgi disruption, HCF-1 rapidly relocalizes to the nucleus, unlike other Golgi-associated proteins; this Golgi sequestration is distinct from the previously proposed ER/CREB3-mediated cytoplasmic retention, and nuclear relocalization correlates with viral reactivation. |
Immunofluorescence in primary neurons and latently infected mice, Golgi disruption experiments, subcellular localization studies |
Journal of virology |
Medium |
18667495
|
| 2010 |
HCF-1 interacts directly and simultaneously with both HSV DNA replication proteins and the cellular histone chaperone Asf1b; Asf1b localizes with HCF-1 at viral replication foci; depletion of Asf1b results in significantly reduced viral DNA accumulation, establishing HCF-1 as a component of the HSV DNA replication assembly that promotes viral DNA replication by coupling Asf1b to replication components. |
Co-immunoprecipitation (direct and simultaneous), immunofluorescence colocalization, siRNA depletion of Asf1b with viral DNA accumulation readout |
Proceedings of the National Academy of Sciences |
Medium |
20133788
|
| 2007 |
Loss of the C. elegans HCF-1 homolog (Ce HCF-1) at reduced temperatures causes embryonic lethality with mitotic and cytokinetic defects; viable mutant embryos display reduced levels of phospho-histone H3 serine 10 (H3S10P); mammalian cells with defective HCF-1 also display defects in mitotic H3S10P status, indicating a conserved role for HCF-1 in regulating mitotic histone phosphorylation. |
C. elegans deletion mutant analysis, immunofluorescence for H3S10P in worms and mammalian cells, tsBN67 temperature-shift experiments |
PloS one |
Medium |
18043729
|
| 2002 |
Inactivation of pRb family members (pRb, p107, p130) by SV40 large T antigen or adenovirus E1A bypasses the requirement for HCF-1 function in tsBN67 cell proliferation and cytokinesis, without restoring HCF-1 chromatin association; this epistasis indicates that HCF-1 regulates cell proliferation and cytokinesis at least in part by opposing pRb family member function. |
Genetic epistasis using SV40 Tag and E1A, tsBN67 complementation assays, pRb family member mutants |
Molecular and cellular biology |
Medium |
12215534
|
| 2013 |
Missense mutations in the HCFC1 Kelch domain cause X-linked cblX disorder; siRNA-mediated knockdown of HCFC1 in fibroblasts leads to coordinate downregulation of MMACHC mRNA; consensus HCFC1 binding sites were identified in the MMACHC promoter, establishing HCFC1 as a transcriptional regulator of MMACHC expression. |
siRNA knockdown, RT-PCR, promoter binding site analysis, patient fibroblast studies |
American journal of human genetics |
Medium |
24011988
|
| 2014 |
Zebrafish hcfc1b regulates cranial neural crest cell differentiation and proliferation within posterior pharyngeal arches; hcfc1b-mediated craniofacial abnormalities were rescued by expression of human MMACHC, establishing that HCFC1 acts upstream of MMACHC in craniofacial development. |
Zebrafish morpholino knockdown, rescue by MMACHC expression, analysis of neural crest cell differentiation/proliferation |
Developmental biology |
Medium |
25281006
|
| 2019 |
HCF-1 is O-GlcNAcylated in response to glucose as a prerequisite for its binding to ChREBP; upon binding, HCF-1 recruits OGT to O-GlcNAcylate ChREBP and activate it; the HCF-1:ChREBP complex resides at lipogenic gene promoters where HCF-1 regulates H3K4 trimethylation and recruits the histone demethylase PHF2 for epigenetic activation of lipogenic genes. |
Co-immunoprecipitation, ChIP, O-GlcNAcylation assays, glucose-responsive cell culture experiments, genetic knockdown |
Molecular cell |
High |
31227231
|
| 2016 |
OGT-mediated glycosylation and HCF-1 proteolysis occur through separable mechanisms within the same active site; a specific TPR domain contact with HCF-1 substrate is critical for proteolysis but not Ser/Thr glycosylation; key catalytic domain residues and UDP-GlcNAc oxygen important for glycosylation are irrelevant for proteolysis; single-activity OGT enzymes (either glycosylase-only or protease-only) can be engineered in vitro and in vivo. |
Active-site mutagenesis, in vitro glycosylation and proteolysis assays, engineered OGT variants |
Genes & development |
High |
27056667
|
| 2015 |
The HCF-1PRO repeat cleavage signal has specific OGT-binding properties; the glutamate at the cleavage site inhibits OGT:UDP-GlcNAc association; a novel OGT-binding sequence adjacent to the first HCF-1PRO repeat enhances cleavage, demonstrating that distinct OGT-binding sites in HCF-1 cooperate to promote proteolysis. |
In vitro OGT binding assays, mutagenesis of cleavage site glutamate, biochemical cleavage assays |
PloS one |
Medium |
26305326
|
| 2018 |
The HCF-1PRO repeat threonine-rich region is tightly bound by the OGT TPR region and activates both OGT glycosylation and proteolysis activities; linkage of this region to heterologous sequences potentiates serine glycosylation with poor OGT co-substrates and enables proteolysis of non-HCF-1PRO cleavage sequences containing an appropriately positioned glutamate. |
In vitro OGT glycosylation and proteolysis assays with chimeric substrates, mutagenesis |
The Journal of biological chemistry |
Medium |
30224358
|
| 2009 |
During the G1-to-S transition, E2F1 associates with HCF-1 through a short DHQY sequence; this HCF-1-binding sequence permits E2F1 to stimulate both DNA damage and apoptosis; HCF-1 and MLL family H3K4 methyltransferases have important functions in E2F1-mediated apoptosis; sequence changes in the E2F1 HCF-1-binding site modulate E2F1-induced apoptosis. |
Mutagenesis of E2F1 DHQY motif, co-immunoprecipitation, apoptosis assays, DNA damage assays, HCF-1 and MLL knockdown |
The EMBO journal |
Medium |
19763085
|
| 2003 |
The HCF-1 binding motif (HBM) occurs in a wide spectrum of DNA-binding proteins and cofactors; Krox20 and E2F4 show strong requirement for functional HCF-1 to activate transcription; in Krox20, the HBM lies in the N-terminal activation domain and its mutation diminishes both transactivation and association with the HCF-1 beta-propeller; the HCF-1C activation domain contributes to Krox20-mediated activation, possibly through recruitment of p300. |
Reporter gene assays, co-immunoprecipitation, mutagenesis of HBM in Krox20 |
The Journal of biological chemistry |
Medium |
14532282
|
| 2012 |
THAP11 physically associates with HCF-1 and recruits HCF-1 to target gene promoters in colon cancer cells; THAP11-mediated gene regulation and chromatin association require HCF-1, while HCF-1 recruitment at THAP11 target genes requires THAP11, demonstrating mutual dependence. |
Co-immunoprecipitation, ChIP, siRNA knockdown of THAP11 and HCF-1, gene expression profiling |
Molecular and cellular biology |
Medium |
22371484
|
| 2015 |
The THAP11/ZNF143/HCFC1 complex is recruited to chromatin through the ACTACA submotif shared by THAP11 and ZNF143; its position, spacing, and orientation relative to the ZNF143 core motif are critical for THAP11 and HCFC1 recruitment to ZNF143-occupied loci; CRISPR-Cas9-mediated alteration of the ACTACA submotif at endogenous promoters reduces THAP11 and HCFC1 binding and alters target gene transcription and histone modifications. |
CRISPR-Cas9 mutagenesis at endogenous promoters, synthetic chromatin-integrated constructs, ChIP, gene expression analysis |
Molecular and cellular biology |
High |
26416877
|
| 2019 |
HSP90 is required for the stability of nuclear HCFC1; HSP90 is required to maintain expression of HCFC1-targeted cell-cycle genes; HSP90 inhibition leads to HCFC1 degradation and consequent downregulation of cell-cycle gene expression. |
Three independent systematic analyses, biochemical co-immunoprecipitation, HSP90 inhibitor treatment, HCFC1 depletion with cell-cycle gene expression analysis |
Cell reports |
Medium |
31693902
|
| 2016 |
HCF-1 conditional knockout in mouse hepatocytes demonstrates that HCF-1 is required for cell-cycle re-entry and proliferation in resting adult liver cells; HCF-1-deficient hepatocytes fail to re-enter the cell cycle during liver regeneration; in embryos, epiblast-specific HCF-1 loss causes cell-cycle exit and apoptosis of HCF-1-negative cells by E8.5. |
Cre-inducible conditional knockout mouse model, liver regeneration model, BrdU incorporation, apoptosis assays, X-chromosome inactivation analysis |
Developmental biology |
High |
26921005
|
| 2016 |
Complete epiblast-specific loss of HCF-1 in male embryos leads to developmental arrest at E6.5 with rapid progressive cell-cycle exit, failure of anterior visceral endoderm migration, failure of primitive streak formation, and absence of gastrulation; the pattern of lethality resembles loss of β-catenin function. |
Conditional knockout mouse model (Hcfc1 epiKO/Y), developmental staging, immunohistochemistry, cell-cycle analysis |
Developmental biology |
High |
27521049
|
| 2021 |
SETD5 regulates RNA polymerase II promoter-proximal pausing on E2F target genes in hematopoietic stem cells in cooperation with HCF-1 and the PAF1 complex; loss of Setd5 disrupts HSC quiescence; HCF-1 co-immunoprecipitates with SETD5. |
Co-immunoprecipitation of SETD5 and HCF-1, conditional knockout mouse model, Pol II ChIP, transcriptome analysis |
Leukemia |
Medium |
34853439
|
| 2020 |
HCF-1 activates CDC42 expression by binding to the -881 to -575 region upstream of the CDC42 transcription start site; overexpression of constitutively active CDC42F28L rescues G1 phase delay and multinucleate defects caused by HCF-1 loss, establishing CDC42 as a functional downstream target of HCF-1 in cell cycle progression. |
ChIP to the CDC42 promoter, siRNA depletion of HCF-1, rescue by constitutively active CDC42, cell cycle and multinucleation assays |
Cell death & disease |
Medium |
33097698
|
| 2013 |
HCF-1 is required for INS-1 pancreatic β-cell glucose-stimulated insulin secretion; HCF-1 reduction causes decreased expression of Pdx1; HCF-1 and E2F1 co-localize at the Pdx1 promoter as shown by ChIP. |
siRNA knockdown, glucose-stimulated insulin secretion assay, RT-PCR for Pdx1, ChIP |
PloS one |
Medium |
24250814
|
| 2024 |
In C. elegans, HCF-1 chromatin localization is largely dependent on functional SET-26; SET-26 and HCF-1 cooperate to regulate a common set of target genes; the histone deacetylase HDA-1 opposes both SET-26 and HCF-1 at a subset of shared target genes and in longevity regulation. |
ChIP, genetic epistasis (set-26, hcf-1, hda-1 mutants), gene expression profiling, lifespan assays |
Nature communications |
Medium |
38485937
|
| 2022 |
Mouse models of Hcfc1 mutation exhibit reduced expression of MMACHC (confirming transcriptional regulation) and additionally show reduced expression of ribosomal protein subunit genes; developmental defects associated with these mutations include aspects of both cblC and ribosomopathies, identifying HCFC1/RONIN as transcriptional regulators of ribosome biogenesis during development. |
Mouse conditional knockout models, RNA-seq, metabolic analysis, developmental phenotyping |
Nature communications |
Medium |
35013307
|
| 2023 |
Conditional deletion of HCF-1 in sensory neurons in vivo causes a striking reduction in latently infected neurons that initiate HSV-1 reactivation; this correlated with a defect in removal of repressive heterochromatin from latent viral genomes, establishing HCF-1 as a critical in vivo regulator that promotes the transition of latent HSV genomes from a repressed chromatin state. |
HCF-1 conditional knockout mouse model, HSV latency/reactivation model, ChIP for repressive chromatin marks, viral reactivation quantification |
mBio |
High |
36692302
|
| 2025 |
Hepatocyte-specific HCF-1 deletion leads to progressive loss of OGT protein levels and global O-GlcNAcylation without altering OGT mRNA, indicating post-translational regulation of OGT stability by HCF-1; loss of HCF-1 reduces nuclear OGT and O-GlcNAcylation, mimicking fasting conditions; HCF-1-negative hepatocytes display cytoplasmic O-GlcNAcylation while HCF-1-positive cells maintain nuclear localization. |
Hepatocyte-specific conditional knockout mouse, immunofluorescence, Western blot, OGT mRNA analysis, fractionation studies |
Scientific reports |
Medium |
40754593
|
| 2026 |
HCF-1 is required for neuronal differentiation and forebrain commissure formation; HCF-1 directly occupies promoters of key neuronal genes (Elavl3, NeuroD1) and its loss reduces activating chromatin marks at these loci; OGT inhibition phenocopies HCF-1 depletion in impairing neuronal proliferation, differentiation, and neurite outgrowth; glycoproteomic analysis reveals disruption of OGT-dependent protein networks involved in neuronal structure. |
Conditional neuronal knockout, ChIP at neuronal gene promoters, siRNA depletion, OGT inhibitor (OSMI-1), glycoproteomics, transcriptomics |
Neurobiology of disease |
Medium |
41651253
|
| 2026 |
HCF-1 binds to the C-terminal ~200 amino acids of ASXL1 and promotes ASXL1 proteasome-dependent turnover; deletion of this ASXL1 C-terminal region abrogates HCF-1 binding and stabilizes ASXL1; HCF-1 and BAP1 show reciprocal antagonism in association with ASXL1, suggesting indirect coupling in complex assembly. |
P2A dual-reporter stability assay, co-immunoprecipitation, proteasome inhibitor experiments, domain deletion mapping |
FASEB journal |
Medium |
41968849
|
| 2024 |
KDM2A recruits E2F1 and HCFC1 to promoters of key meiosis genes (Stra8, Meiosin, Spo11, Sycp1) in male germ cells; conditional deletion of Kdm2a disrupts H3K36me2/3 deposition and impairs expression of HCFC1-recruited target genes required for meiotic entry and progression. |
Co-immunoprecipitation of KDM2A-E2F1-HCFC1, ChIP at meiotic gene promoters, conditional knockout mouse, H3K36me2/3 analysis |
The EMBO journal |
Medium |
39160277
|
| 1999 |
A second HCF-like protein HCF-2 was identified; chimeric protein analysis showed that differences between the fifth and sixth kelch repeats of the beta-propeller domains of HCF-1 and HCF-2 determine selective recruitment of HCF-1 over HCF-2 by VP16 and LZIP. |
Chimeric protein construction, in vitro binding assays, VP16-induced complex assembly assays |
Journal of virology |
Medium |
10196288
|
| 2025 |
RONIN (THAP11) modulates TFEB transcriptional activity through its interaction with HCF-1/HCFC1; RONIN overexpression improved autophagy levels, lysosomal activity, and attenuated D-galactose-induced hair cell senescence, working through TFEB activation. |
Co-immunoprecipitation of RONIN and HCF1, overexpression studies, autophagy/lysosomal activity assays, hair cell senescence model |
Advanced science |
Medium |
39985193
|
| 2024 |
HSP90 N-terminal inhibition reduces HCFC1 protein levels, preventing HCFC1 from binding to the TFEB proximal promoter; decreased TFEB transcription then reduces LC3 levels and promotes mitochondria-derived vesicle (MDV) formation and tumor metastasis; re-activation of the HCFC1-TFEB-LC3 axis by blocking MDV formation suppresses metastasis. |
ChIP for HCFC1 at TFEB promoter, HSP90 inhibitor treatment, HSP90AA1-HCFC1 co-immunoprecipitation, TFEB/LC3 Western blot, MDV formation assays |
Autophagy |
Medium |
39461872
|