| 2005 |
CEP55 localizes to the mother centriole during interphase; Erk2/Cdk1-dependent phosphorylation at S425/S428 triggers centrosome dissociation upon mitotic entry. This phosphorylation enables interaction with Plk1, which then phosphorylates CEP55 at S436. Phosphorylation at S425/S428/S436 is required for CEP55 recruitment to the midbody and for cytokinesis completion; phosphorylation-deficient mutants cause cytokinesis failure. |
Site-directed mutagenesis, in vitro kinase assays, siRNA knockdown, live-cell imaging, co-immunoprecipitation |
Developmental cell |
High |
16198290
|
| 2006 |
CEP55 is a microtubule-associated protein that bundles microtubules in vitro. CEP55 directly binds MKLP1 in vitro and associates with the MKLP1-MgcRacGAP centralspindlin complex in vivo. Centralspindlin knockdown abolishes CEP55 localization to the spindle midzone, placing CEP55 downstream of centralspindlin. CEP55 depletion causes loss of the Flemming body and mislocalization of midbody components, and blocks cell abscission by preventing correct endobrevin (v-SNARE) localization. |
In vitro microtubule bundling assay, in vitro binding assay, co-immunoprecipitation, siRNA knockdown, immunofluorescence microscopy |
Molecular biology of the cell |
High |
16790497
|
| 2006 |
CEP55 homodimerizes, as demonstrated by co-immunoprecipitation. CEP55 localizes to the centrosome throughout mitosis and additionally appears at the cleavage furrow in late anaphase and at the midbody during cytokinesis. Association with the centrosome is microtubule-independent (not disrupted by nocodazole or taxol), suggesting direct interaction with centrosome components. |
Co-immunoprecipitation, immunofluorescence of endogenous and EGFP-tagged CEP55, nocodazole/taxol treatment, microtubule regrowth assay |
Genomics |
Medium |
16406728
|
| 2008 |
The EABR (ESCRT and ALIX-binding region) of CEP55 forms an aberrant dimeric parallel coiled coil with a single binding site for either an ALIX peptide or the TSG101 (ESCRT-I subunit) peptide; the two peptides compete for the same site. Crystal structure solved at 2.0 Å resolution. Both ALIX and ESCRT-I are required for cytokinesis, implying multiple CEP55 dimers act together. |
X-ray crystallography (2.0 Å), biochemical competition assays with peptides, functional cytokinesis assays |
Science (New York, N.Y.) |
High |
18948538
|
| 2009 |
CEP55 (FLJ10540) forms a complex with the PI3K catalytic subunit (p110α) and can activate PI3K activity, leading to AKT pathway activation and oncogenic cell transformation (anchorage-independent growth, tumorigenesis in nude mice). |
Co-immunoprecipitation, PI3K activity assay, soft-agar colony formation, nude mouse xenograft, siRNA knockdown |
Oncogene |
Medium |
17237822
|
| 2009 |
Pin1 (peptidyl-prolyl isomerase) localizes to the midbody ring and binds CEP55; this interaction promotes Plk1-mediated phosphorylation of CEP55, which is critical for cytokinesis. Pin1 knockout MEFs show cytokinesis delay; Pin1 knockdown does not enhance the defect in CEP55-depleted cells, placing Pin1 and CEP55 in the same cytokinesis pathway. |
Co-immunoprecipitation, siRNA knockdown, Pin1-KO MEFs, immunofluorescence, genetic epistasis |
Cancer research |
High |
19638580
|
| 2009 |
VEGF-A stimulation of lung cancer cells increases CEP55 (FLJ10540) protein expression and enhances its complex formation with PI3K. CEP55 knockdown destabilizes the p110α/p85α PI3K complex. CEP55 mediates cell migration and invasion downstream of VEGFR2 via the PI3K/AKT pathway. |
Co-immunoprecipitation, siRNA knockdown, migration/invasion assays, VEGFR2 and PI3K inhibitor treatment, western blot |
PloS one |
Medium |
19337377
|
| 2009 |
CEP55 stability is post-translationally regulated during mitosis; Pin1 knockdown or mutation of Pin1 binding sites in CEP55 reduces its stability. Plk1 phosphorylation site mutation lowers CEP55 stability, while Plk1 overexpression increases CEP55 levels, indicating Pin1 regulates Plk1-mediated phosphorylation to stabilize CEP55 during mitosis. |
siRNA knockdown, site-directed mutagenesis, Plk1 overexpression, western blot for protein stability |
Cell cycle (Georgetown, Tex.) |
Medium |
19855176
|
| 2010 |
TEX14 uses an evolutionarily conserved GPPX3Y motif to bind CEP55 and competitively block ALIX and TSG101 (which use similar GPPX3Y motifs) from interacting with CEP55 at the midbody. This diverts CEP55 from promoting abscission to stabilizing intercellular bridges in male germ cells, thereby arresting cytokinesis and forming stable intercellular bridges required for spermatogenesis. |
Biochemical enrichment of intercellular bridges, co-immunoprecipitation, in vitro binding competition assay, TEX14-KO mice |
Molecular and cellular biology |
High |
20176808
|
| 2010 |
Plk1 phosphorylates CEP55 in trans during the metaphase-to-anaphase transition, preventing premature recruitment of CEP55 to the anaphase spindle. Only after Plk1 is degraded during mitotic exit can CEP55 target the midbody to promote abscission. A phosphorylation-site mutant of CEP55 is prematurely recruited to the anaphase spindle and fails to support abscission. Blocking Plk1 degradation (elevated midbody Plk1) prevents CEP55 recruitment. |
Plk1 inhibitors (BI2536, GW842862), phosphorylation-site mutagenesis, time-lapse imaging, siRNA knockdown |
The Journal of cell biology |
High |
21079244
|
| 2010 |
CEP55 and pericentrin localize to intercellular bridges in mouse testis spermatogenic cells, forming a double-ring structure (inner ring: CEP55/pericentrin; outer ring: MKLP1), suggesting CEP55 is required for stable intercellular bridges during spermatogenesis and spermiogenesis. |
Immunofluorescence microscopy, confocal imaging of testis tissue sections |
Journal of cellular biochemistry |
Medium |
20186884
|
| 2011 |
p53 negatively regulates CEP55 protein stability and promoter activity. This occurs through repression of Plk1 levels; Plk1 is a positive regulator of CEP55 post-translational stability. Overexpression of Plk1 or knockdown of p53 both enhance CEP55 stability; Plk1 inhibitor BI2356 prevents CEP55 accumulation in p53-knockdown cells, establishing a p53–Plk1–CEP55 axis. |
Plk1 overexpression, p53 knockdown/induction, Plk1 inhibitor treatment, promoter-luciferase assay, western blot for protein stability |
The Journal of biological chemistry |
High |
22184120
|
| 2012 |
BRCA2 is recruited to the midbody through interaction with Filamin A actin-binding protein. At the midbody, BRCA2 facilitates formation of CEP55–ALIX and CEP55–TSG101 complexes required for abscission. Cancer-associated BRCA2 mutations that disrupt Filamin A interaction increase cytokinetic defects without affecting homologous recombination, defining a separate cytokinetic role for BRCA2 upstream of CEP55 complex assembly. |
Co-immunoprecipitation, immunofluorescence, siRNA knockdown, BRCA2 cancer-mutation constructs |
Developmental cell |
High |
22771033
|
| 2015 |
CEP55 is required for spindle organization and meiotic cell cycle progression in mouse oocytes. CEP55 localizes to meiotic spindle poles at metaphase and to the midbody at telophase. CEP55 knockdown causes dissociation of γ-tubulin from spindle poles, severely defective spindles, chromosome misalignment, metaphase I arrest, failure of first polar body extrusion, cyclin B accumulation, and spindle assembly checkpoint activation. |
siRNA microinjection in oocytes, immunostaining, confocal microscopy, time-lapse live imaging of GFP-Cep55 mRNA-injected oocytes |
Scientific reports |
Medium |
26582107
|
| 2015 |
Cep55 loss-of-function in zebrafish (nonsense mutant and morpholino) causes apoptosis and cell cycle defects; Akt is destabilized in homozygous cep55 mutants. Expression of constitutively active PIK3CA or AKT1 partially rescues the mutant phenotype. Proteasome inhibitor MG132 also partially rescues, indicating CEP55 promotes Akt stability by protecting it from proteasomal degradation. |
Zebrafish cep55 nonsense mutant, morpholino knockdown, constitutively active PIK3CA/AKT1 rescue, MG132 treatment, western blot for Akt levels |
FASEB journal |
High |
25667221
|
| 2016 |
FAK-Src signaling downstream of integrin-mediated cell adhesion decelerates PLK1 degradation at the midbody, thereby controlling the timing of CEP55 accumulation at the midbody. In non-adherent cells, PLK1 disappears from the midbody more rapidly, preventing CEP55 from efficiently recruiting ALIX, TSG101, and CHMP4B to complete abscission. |
FAK/Src inhibitors, adhesion assays, immunofluorescence of midbody proteins, time-lapse imaging |
Oncotarget |
Medium |
27127172
|
| 2017 |
A truncating (nonsense) mutation in CEP55 causes MARCH syndrome. Truncated CEP55 protein fails to localize to the midbody in human cells, resulting in abscission failure and multinucleated daughter cells. Suppression of cep55l in zebrafish recapitulates MARCH features (renal dysplasia, cerebellar hypoplasia, craniofacial abnormalities); full-length but not truncated human CEP55 mRNA rescues these phenotypes. |
Patient-derived cell immunofluorescence for midbody localization, zebrafish cep55l morpholino, mRNA rescue experiments (full-length vs truncated) |
Journal of medical genetics |
High |
28264986
|
| 2018 |
iASPP acts as a PP1-targeting subunit to facilitate interaction between the phosphatase PP1 and CEP55, enabling removal of PLK1-mediated Ser436 phosphorylation from CEP55 during late mitosis. This dephosphorylation is critical for timely CEP55 recruitment to the midbody. iASPP depletion results in abnormal midbody structure and failed cytokinesis. |
Protein affinity purification, co-immunoprecipitation, phosphorylation assays, siRNA knockdown, immunofluorescence |
Cell death & disease |
High |
29743530
|
| 2018 |
CEP55 overexpression in transgenic mice causes hyperactivation of PI3K/Akt signaling in testis, increased FoxO1 phosphorylation and suppression of its nuclear retention, upregulation of Ret proto-oncogene and Gfra1, and selective downregulation of germ cell differentiation genes (Egr4, Sohlh1), resulting in spermatogenic arrest and male sterility. |
Ubiquitously overexpressing Cep55 transgenic mice, western blot, immunofluorescence, qPCR for downstream targets |
FASEB journal |
High |
29683733
|
| 2018 |
SPAG5 interacts with CEP55 to trigger phosphorylation of AKT at Ser473. This interaction promotes HCC tumor growth and metastasis. Inhibition of PI3K/AKT signaling attenuates SPAG5-mediated cell growth. |
Co-immunoprecipitation, western blot for pAKT-Ser473, siRNA knockdown, in vitro and in vivo tumor models |
Molecular cancer |
Medium |
30089483
|
| 2018 |
CEP55 physically interacts with JAK2 and promotes its phosphorylation, activating JAK2–STAT3 signaling and upregulating downstream MMP2/9. Blocking JAK2 or STAT3 blunts CEP55-overexpression-driven HCC cell migration and invasion. |
Co-immunoprecipitation, western blot for pJAK2/pSTAT3, JAK2/STAT3 inhibitors, siRNA knockdown, migration/invasion assays |
Cells |
Medium |
30096813
|
| 2018 |
CEP55 is a downstream effector of the MEK1/2-MYC axis. Loss of CEP55 sensitizes breast cancer cells to anti-mitotic agents through premature CDK1/cyclin B activation and CDK1 caspase-dependent mitotic cell death. Blocking MEK1/2-PLK1 signaling reduces CEP55 levels and restricts tumor outgrowth in syngeneic and xenograft breast tumor models. |
CEP55 KD/OE in cell lines, MEK1/2 and PLK1 inhibitors, flow cytometry for CDK1/cyclin B activation and apoptosis, in vivo tumor models, western blot |
EMBO molecular medicine |
High |
30108112
|
| 2019 |
First meiotic anaphase requires Cep55-dependent inhibitory CDK1 phosphorylation. Cep55-depleted mouse oocytes fail anaphase I due to persistent CDK1 activity despite on-time SAC silencing and intact APC-mediated proteolysis. Impaired CDK1 inactivation results from failure to suppress Cdc25 phosphatase, identifying a proteolysis-independent CDK1 inactivation step in meiosis I. |
siRNA depletion in mouse oocytes, CDK1 kinase activity assay, immunoblotting for Cdc25/CDK1 phosphorylation, time-lapse imaging |
Journal of cell science |
High |
31427428
|
| 2019 |
CEP55 contains two NEMO-like ubiquitin-binding domains (NOA and ZF). In vitro, the NOA domain forms a dimeric coiled-coil and the ZF domain adopts a UBZ scaffold. Structure-guided mutations in either NOACEP55 or ZFCEP55 that abolish ubiquitin binding cause severe abscission defects in CEP55-knockdown cells reconstituted with these mutants. The ZFCEP55 function can be substituted by other UBZ-family domains, establishing its role as a ubiquitin receptor essential for cytokinetic abscission. |
In vitro structural studies of isolated domains, structure-guided mutagenesis, siRNA knockdown with reconstitution, abscission assays |
iScience |
High |
31605944
|
| 2020 |
Cep55 is dispensable for cytokinesis in most mammalian cell types and tissues but is specifically required for neural progenitor cell abscission. Cep55-KO mice show microcephaly but near-normal body size; primary neural progenitors require Cep55 and ESCRT for survival and abscission. Primary fibroblasts divide without Cep55 and ESCRT-III at the midbody, establishing that Cep55-independent cell division occurs in non-neural contexts. |
Cep55-knockout mouse model, primary cell cultures (NSCs, fibroblasts), live-cell imaging of abscission, ESCRT depletion in primary cells |
Nature communications |
High |
32269212
|
| 2020 |
Cep55 overexpression in transgenic MEFs induces a compromised Chk1-dependent S-phase checkpoint, increased replication speed and DNA damage, and aberrant mitotic division. This phenotype is rescued by PI3K/Akt inhibition or by expression of Akt-insensitive Chk1 (S280A), placing the mechanism as: Cep55→hyperactivated Pi3k/Akt→Akt-mediated Chk1 inhibition→replication stress→genomic instability. Cep55 overexpression also causes stabilized microtubules. |
Cep55-transgenic MEFs, PI3K/Akt inhibitors, Chk1-S280A rescue expression, DNA fiber assay, immunofluorescence for microtubule stability |
Communications biology |
High |
33087841
|
| 2021 |
Cep55 loss in mouse cortical neural stem cells (NSCs) slows abscission and increases failure rate; failed abscission in NSCs (but not fibroblasts) activates p53, leading to tissue-specific apoptosis and microcephaly. Double KO of Cep55 and p53 blocks apoptosis but only partially rescues brain size, indicating additional p53-independent cell cycle exit defects. CEP55 facilitates ESCRT recruitment and timely microtubule disassembly at the midbody. |
Cep55-KO and Cep55/p53 double-KO mice, quantitative live and fixed imaging of abscission in cortical NSCs and fibroblasts, ESCRT recruitment assays |
The Journal of neuroscience |
High |
33622776
|
| 2021 |
CEP55 promotes cilia disassembly by interacting with and stabilizing Aurora A kinase, which is achieved by facilitating the chaperonin CCT complex to Aurora A. Cep55-KO mice display Meckel-Gruber syndrome features including perinatal death, polycystic kidneys, CNS abnormalities, and abnormal cilia elongation. CEP55 mutations causing Meckel-Gruber syndrome impair cilia disassembly. |
Cep55-KO mice, co-immunoprecipitation of CEP55-Aurora A-CCT complex, immunofluorescence for cilia length, western blot for Aurora A stability |
The Journal of cell biology |
High |
33475699
|
| 2022 |
NEDD4L E3 ubiquitin ligase targets CEP55 for ubiquitination and degradation. miR-342-3p delivered by M2 macrophage exosomes suppresses NEDD4L, thereby inhibiting CEP55 ubiquitination and elevating CEP55 protein expression, activating PI3K/AKT/mTOR signaling to promote RCC growth and metastasis. |
miRNA-binding assays, NEDD4L-CEP55 ubiquitination assay, western blot for CEP55 protein levels upon NEDD4L modulation, in vivo tumor models |
Oncology research |
Medium |
37305161
|
| 2023 |
α-catenin physically interacts with CEP55 in the cytoplasm of HCC cells (identified by BioID/mass spectrometry and confirmed by proximity ligation assay and co-immunoprecipitation). This interaction stabilizes CEP55 protein. Additionally, a FoxM1/TEAD/YAP transcriptional complex independently transcriptionally induces CEP55. CEP55 supports HCC cell migration in conjunction with α-catenin, but does not affect HCC cell proliferation. |
BioID proximity labeling + mass spectrometry, proximity ligation assay, co-immunoprecipitation, chromatin immunoprecipitation, siRNA knockdown, migration assays |
Cell communication and signaling : CCS |
High |
37381005
|
| 2024 |
ALKBH5-mediated m6A demethylation induces mRNA degradation of the transcription factor FOXP2. FOXP2 binds the CEP55 promoter to repress CEP55 transcription. ALKBH5 knockdown therefore increases FOXP2 stability, which represses CEP55, inducing cell cycle arrest and inhibiting EMT in ovarian cancer cells. |
ChIP assay (FOXP2 binding at CEP55 promoter), dual-luciferase reporter assay, ALKBH5 knockdown, m6A analysis, cell cycle and EMT assays |
Biology direct |
Medium |
39511642
|
| 2025 |
Endogenous CEP55 appears as dot-like structures in cancer cells and localizes to secretory late CD63-positive endosomes (not to early Rab5- or late Rab7-positive endosomes) and associates with Alix dots. Mutation of the CEP55–Alix interaction site strongly reduces CEP55 dot formation and CEP55 loading into extracellular vesicles, establishing that CEP55 is delivered to exosomes via Alix-mediated recruitment to secretory late endosomes rather than the canonical early-to-late endosome pathway. |
High-resolution microscopy (EGFP-CEP55 trafficking), co-localization with Rab5/Rab7/CD63 markers, Alix-interaction site mutagenesis, western blot of exosome fractions |
Journal of extracellular vesicles |
Medium |
39976236
|
| 2025 |
CEP55 interacts with TPX2 (co-immunoprecipitation) to activate the Aurora A kinase (AURKA)–PI3K–AKT signaling cascade in prostate cancer cells. This activation upregulates SLC7A11 and GPX4, reduces lipid ROS, and confers resistance to ferroptosis. Pharmacological inhibition of the TPX2–AURKA interaction (CAM2602) reverses these effects. In vivo, CEP55 knockdown reduces tumor growth and downregulates this pathway. |
Co-immunoprecipitation (CEP55–TPX2), western blot for AURKA/pAKT/SLC7A11/GPX4, lipid ROS measurement, TPX2-AURKA inhibitor CAM2602, xenograft tumor model |
The Journal of biological chemistry |
Medium |
41617029
|
| 2025 |
USP8 deubiquitinase stabilizes CEP55 protein through deubiquitination. CEP55 in turn binds CHMP6 (co-immunoprecipitation) and promotes CHMP6 expression, inhibiting ferroptosis and promoting macrophage M2 polarization and malignant behaviors in TNBC cells. USP8 knockdown effects on tumor growth are reversed by CEP55 overexpression in vivo. |
Co-immunoprecipitation (CEP55–CHMP6), ubiquitination/immunoprecipitation assay (USP8–CEP55), western blot for ferroptosis markers (Fe2+, MDA, GSH, ROS), xenograft tumor model |
Clinical breast cancer |
Medium |
40925844
|
| 2025 |
ILF3 (RNA-binding protein) stabilizes CEP55 mRNA, as validated by RNA immunoprecipitation and mRNA stability assay. ILF3 depletion reduces CEP55 protein and impairs breast cancer cell growth, invasion, and migration while promoting ferroptosis and apoptosis. CEP55 restoration partially rescues the malignant defects of ILF3-depleted cells. |
RNA immunoprecipitation (RIP), CEP55 mRNA stability assay, siRNA knockdown, transwell and flow cytometry assays, xenograft model |
Hereditas |
Medium |
39871389
|