| 2010 |
USP44 encodes a catalytically active deubiquitinating enzyme that can cleave ubiquitin from ubiquitinated substrates both in vitro and in vivo. USP44 itself undergoes K48- and K63-linked polyubiquitination. The protein contains a ZnF-UBP domain and conserved catalytic residues (Cys, His, Asn/Asp). Subcellular localization studies showed predominant nuclear expression. |
In vitro deubiquitinase assay, in vivo ubiquitination assay, in situ hybridization, RT-PCR, immunofluorescence/localization |
Cell biology international |
Medium |
20402667
|
| 2012 |
USP44 is a key regulator of APC/C activation during the mitotic checkpoint. Overexpression of USP44 promotes association of Mad2 with Cdc20, reinforcing the mitotic checkpoint, and stabilizes cyclin B1 in G2. High USP44 causes chromosome segregation errors and aneuploidy in non-transformed cells. |
Overexpression in murine embryonic fibroblasts, co-immunoprecipitation (Mad2-Cdc20 interaction), chromosome analysis, cyclin B1 degradation assays |
PloS one |
Medium |
21853124
|
| 2012 |
USP44 negatively regulates H2B monoubiquitination (H2Bub1) on lysine 120, acting as a deubiquitinase that opposes RNF20-mediated H2B ubiquitylation. Downregulation of USP44 during embryonic stem cell differentiation contributes to the increase in H2Bub1 required for efficient differentiation, particularly for transcriptional induction of long genes. |
USP44 knockdown/overexpression in ESCs, H2Bub1 ChIP, gene expression analysis, RNF20/USP44 epistasis |
Molecular cell |
High |
22681888
|
| 2012 |
USP44 prevents chromosome segregation errors by regulating centrosome separation, positioning, and mitotic spindle geometry through direct binding to the centriole protein centrin. This function is independent of its role in the mitotic checkpoint. Usp44-knockout mice develop spontaneous tumors. |
Usp44 knockout mouse engineering, chromosome lagging assays, centrosome positioning analysis, direct binding assay with centrin, mitotic spindle geometry measurements |
The Journal of clinical investigation |
High |
23187126
|
| 2013 |
USP44 is recruited to RNF168-generated ubiquitylation products at DNA double-strand break (DSB) sites and promotes efficient deubiquitylation of histone H2A. USP44 overexpression powerfully inhibits RNF8/RNF168-mediated 53BP1 retention at DSBs by reducing RNF168 accrual. Unlike USP29, USP44's activity is specific to ubiquitylated H2A. |
DUB overexpression screen, immunofluorescence for 53BP1 and RNF168 foci at DSBs, H2A deubiquitylation assay, USP44 depletion experiments |
The Journal of biological chemistry |
High |
23615962
|
| 2016 |
USP44 is an integral subunit of the nuclear receptor co-repressor (N-CoR) complex. Within this complex, USP44 directly deubiquitinates histone H2B in vitro and in vivo. Ablation of USP44 impairs the repressive activity of N-CoR. ChIP confirmed that USP44 recruitment reduces H2Bub1 at N-CoR target loci. USP44 depletion also impairs invasiveness of triple-negative breast cancer cells and increases global H2Bub1. |
Mass spectrometry identification of N-CoR complex components, co-immunoprecipitation, in vitro H2B deubiquitylation assay, ChIP, USP44 knockdown with invasion assay |
Cell reports |
High |
27880911
|
| 2019 |
USP44 interacts with EZH2 and prevents its ubiquitination and proteasomal degradation, thereby stabilizing EZH2 protein and maintaining its gene silencing (H3K27 methyltransferase) activity. USP44 knockdown reduces EZH2 protein levels and inhibits tumorigenic characteristics of prostate cancer cells; ectopic EZH2 rescues the knockdown phenotype. |
Co-immunoprecipitation, ubiquitination assay, USP44 knockdown/rescue with EZH2, in vitro and in vivo tumor assays |
Molecules and cells |
Medium |
30622230
|
| 2019 |
USP44 promotes deubiquitination of FBP1 (fructose-1,6-bisphosphatase), increasing FBP1 protein expression in pancreatic cancer cells, which suppresses aerobic glycolysis and inhibits tumor progression and gemcitabine resistance. |
Co-immunoprecipitation, ubiquitination assay, USP44 overexpression/knockdown with FBP1 protein level measurement, cell proliferation and drug resistance assays |
American journal of cancer research |
Medium |
31497353
|
| 2020 |
USP44 interacts with and stabilizes FOXP3 in induced regulatory T cells (iTregs) by removing K48-linked ubiquitin modifications, preventing proteasomal degradation of FOXP3. TGF-β induces USP44 expression during iTreg differentiation. USP44 cooperates with USP7 to stabilize FOXP3. Tregs lacking USP44 show reduced suppressive function in vitro and in vivo. |
Co-immunoprecipitation, ubiquitination assay, USP44 genetic knockout in Tregs, in vitro Treg suppression assays, in vivo inflammatory models |
EMBO reports |
High |
32644293
|
| 2020 |
USP44 is recruited to MITA/STING following DNA virus infection and removes K48-linked polyubiquitin moieties from MITA at K236, preventing proteasome-mediated degradation of MITA and sustaining innate antiviral signaling (type I IFN and pro-inflammatory cytokine induction). USP44-deficient mice show accelerated HSV-1-induced MITA degradation, reduced interferon induction, and greater susceptibility to HSV-1. |
Co-immunoprecipitation, ubiquitination assay (K48 linkage-specific), USP44-deficient mouse model, viral titer measurement, cytokine induction assays |
PLoS pathogens |
High |
31968013
|
| 2020 |
USP44 overexpression increases Axin1 protein (but not mRNA) levels by interacting with Axin1 and reducing its ubiquitination, thereby stabilizing Axin1 and inactivating the Wnt/β-catenin pathway. Axin1 knockdown abolishes the anti-proliferative and pro-apoptotic effects of USP44 in colorectal cancer cells. |
Co-immunoprecipitation, ubiquitination assay, Axin1 knockdown rescue experiment, Wnt/β-catenin pathway target protein western blot |
Cell biology international |
Medium |
32285989
|
| 2021 |
USP44 directly deubiquitinates DDB2 to prevent its premature proteasomal degradation, selectively facilitating repair of UV-induced cyclobutane pyrimidine dimers (CPDs) through nucleotide excision repair (NER). Cells lacking USP44 show impaired DDB2 accumulation on DNA lesions and defective XPC retention. Usp44-null mice are prone to DMBA- and UV-induced tumors. |
In vitro deubiquitylation assay, USP44 KO cell lines and mouse models, ChIP/live-cell imaging of DDB2/XPC at lesions, tumor induction experiments |
Frontiers in cell and developmental biology |
High |
33937266
|
| 2022 |
USP44 recruits and stabilizes the E3 ubiquitin ligase TRIM25 by removing K48-linked polyubiquitin chains at Lys439 of TRIM25. Stabilized TRIM25 then promotes degradation of Ku80, inhibiting its recruitment to DSBs and suppressing NHEJ DNA repair, thereby enhancing radiosensitivity. |
Co-immunoprecipitation, ubiquitination assay (K48 linkage, specific site Lys439), TRIM25 knockout rescue experiments, Ku80 recruitment assays at DSBs, in vitro and in vivo radiosensitivity assays |
Nature communications |
High |
35079021
|
| 2022 |
USP44 interacts with WDR5 and represses its K48-linked ubiquitination and proteasomal degradation, stabilizing WDR5 protein. This interaction promotes T-ALL cell proliferation and survival; WDR5 overexpression rescues apoptosis induced by USP44 knockdown. |
Co-immunoprecipitation, co-localization, ubiquitination assay, USP44 knockdown/overexpression, WDR5 rescue experiments, in vivo xenograft |
International journal of medical sciences |
Medium |
36483601
|
| 2023 |
USP44 directly interacts with Itch (an E3 ligase in Hedgehog signaling) and promotes its deubiquitination and stabilization. Stabilized Itch promotes proteasomal degradation of Gli1, thereby inactivating Hedgehog signaling and suppressing PDL1 expression in hepatocellular carcinoma. |
Quantitative proteomics, co-immunoprecipitation, ubiquitination assay, USP44 knockdown/overexpression, Gli1 and PDL1 measurement, in vitro and in vivo tumor assays |
Cell death & disease |
Medium |
38097536
|
| 2023 |
MAD2 sequesters USP44 in the nucleus of cholangiocarcinoma cells, impairing formation of the USP44/LIMA1 complex in the cytoplasm and enhancing K48-linked ubiquitination and degradation of LIMA1, thereby activating the IGF1R/PI3K/AKT pathway and promoting cancer progression. |
Co-immunoprecipitation, ubiquitination assay, subcellular fractionation, USP44/LIMA1 complex analysis, AKT pathway readout |
Oncogene |
Medium |
37752233
|
| 2024 |
USP44 directly interacts with p21 (CDKN1A) and eliminates its K48-linked polyubiquitin chain in a cell cycle-independent manner, stabilizing p21 protein. This stabilization suppresses the G1/S transition and inhibits thyroid cancer cell proliferation; rescue of p21 partially reverses the effects of USP44 depletion. |
Co-immunoprecipitation, ubiquitination assay (K48-specific), USP44 knockdown/rescue with p21, cell cycle analysis, in vitro and in vivo proliferation assays |
International journal of biological sciences |
Medium |
39430240
|
| 2024 |
USP44 directly interacts with BRCA2 in neuroblastoma cells, as established by proximity biotinylation (BioID) proteomics and validated by immunoprecipitation. Cells lacking USP44 show increased chromosome breaks and radial chromosomes after mitomycin C treatment, indicating a role for USP44 in the Fanconi anemia DNA repair pathway. |
BioID proximity biotinylation mass spectrometry, immunoprecipitation validation, chromosome breakage analysis in USP44-null cells after MMC treatment |
Biomedicines |
Medium |
39767807
|
| 2024 |
USP44 interacts with HEXIM1 and enhances HEXIM1 protein stability. Silencing HEXIM1 enhances the malignant phenotype of OSCC cells and reverses the antitumor effects of USP44 overexpression, placing HEXIM1 downstream of USP44. |
Co-IP mass spectrometry, label-free quantitative LC-MS/MS proteomics, co-immunoprecipitation, USP44 overexpression/knockdown, HEXIM1 knockdown rescue |
Biology direct |
Medium |
39722007
|
| 2024 |
USP44 stabilizes ITGB4 via deubiquitination, and this prevents cisplatin resistance in gastric cancer cells by modulating ROS and the MAPK/NF-κB pathway. ITGB4 affects P-gp expression and antioxidant enzyme activity through MAPK/NF-κB signaling. |
Proteomic analysis, co-immunoprecipitation, ubiquitination assay, USP44 overexpression/knockdown, ROS measurement, MAPK/NF-κB pathway readouts |
FASEB journal |
Low |
40824171
|
| 2025 |
USP44 recruits and stabilizes STUB1 (CHIP E3 ligase) by removing K48-linked polyubiquitin chains at Lys30 of STUB1. Stabilized STUB1 promotes K48-linked polyubiquitination of LRPPRC at Lys453 and its degradation, increasing mitochondrial ROS accumulation and cisplatin-induced apoptosis in neuroblastoma. |
Co-immunoprecipitation, ubiquitination assay (K48 linkage, site-specific at Lys30 and Lys453), USP44 overexpression/knockdown, LRPPRC rescue experiments, mROS measurement |
Neuro-oncology |
Medium |
39215663
|
| 2025 |
EGR1 transcriptionally induces USP44 expression in cigarette smoke-exposed lung epithelial cells. USP44 then deubiquitinates and stabilizes TRAF6, promoting NLRP3 inflammasome-mediated pyroptosis. Inhibition of either EGR1 or USP44 reduces CSE-induced pyroptosis and alleviates COPD-like pathology in mice. |
Transcriptome sequencing, co-immunoprecipitation, ubiquitination assay, EGR1/USP44 knockdown in cellular and animal COPD models, pyroptosis assays (PI staining, caspase-1/GSDMD western blot) |
Journal of inflammation research |
Medium |
41333036
|
| 2025 |
USP44 interacts with EZH2 in triple-negative breast cancer cells, preventing EZH2 ubiquitination and proteasomal degradation, thereby promoting chemotherapy resistance. The EZH2 inhibitor GSK126 reverses the chemoresistance induced by USP44 overexpression. |
Co-immunoprecipitation, ubiquitination assay, USP44 knockdown/overexpression, EZH2 inhibitor treatment, in vivo xenograft models |
Cancer biology & therapy |
Medium |
40619273
|
| 2025 |
USP44 interacts with SENP2 and stabilizes it through deubiquitination, thereby inhibiting esophageal squamous cell carcinoma invasion and metastasis. Knockdown of SENP2 reduces the inhibitory effect of USP44 on ESCC cell migration. |
Liquid chromatography-mass spectrometry, co-immunoprecipitation, cycloheximide chase assay, ubiquitination analysis, USP44 overexpression/knockdown in vitro and in vivo |
Clinical epigenetics |
Medium |
41250203
|
| 2025 |
USP44 stabilizes MAOB (monoamine oxidase B) via deubiquitination in lung adenocarcinoma cells. The USP44-MAOB axis inhibits cisplatin resistance and malignant phenotypes; MAOB knockdown reverses USP44-mediated effects on DDP sensitivity. |
Co-immunoprecipitation, cycloheximide (CHX) chase assay, ubiquitination assay, USP44 overexpression/knockdown, MAOB knockdown rescue |
International journal of genomics |
Low |
42183175
|
| 2025 |
USP44 protein delivered via bone marrow mesenchymal stem cell-derived extracellular vesicles stabilizes RBM14 through deubiquitination, protecting epididymal cells from radiation-induced DNA damage, apoptosis, and oxidative stress. Silencing USP44 in donor MSCs abrogates these protective effects. |
USP44 deubiquitination assay, USP44 knockdown in MSCs/EVs, RBM14 protein stability assay, cell viability, apoptosis, and DNA damage assays in irradiated cells |
Stem cell research & therapy |
Low |
41299552
|