| 2018 |
TUFT1 physically interacts with RABGAP1 (a Rab GTPase activating protein), thereby modulating intracellular lysosomal positioning and vesicular trafficking, and promotes mTORC1 signaling activation. |
Co-immunoprecipitation, cellular fractionation/lysosomal positioning assays, mTORC1 activity assays with TUFT1 knockdown/overexpression |
Cell discovery |
High |
29423269
|
| 2018 |
TUFT1 promotes HCC cell growth, metastasis and epithelial-mesenchymal transition via activation of the Ca2+/PI3K/AKT pathway. Hypoxia upregulates TUFT1 through HIF-1α-dependent downregulation of miR-671-5p, which targets the 3'-UTR of TUFT1 mRNA. |
MTT, BrdU, Transwell assays, subcutaneous/tail vein xenograft models, chromatin immunoprecipitation (HIF-1α binding to TUFT1 promoter), microRNA array, luciferase reporter (miR-671-5p/TUFT1 3'-UTR), western blot for pathway activation |
Oncogene |
Medium |
30250300
|
| 2016 |
TUFT1 promotes pancreatic cancer EMT by altering expression of Snail and is associated with HIF1 expression and activity, suggesting TUFT1 regulates EMT via a HIF1-Snail signaling axis. |
shRNA knockdown and overexpression, migration/invasion assays, in vivo metastasis models, western blot for EMT markers (E-cadherin, vimentin, Snail), HIF1 activity assays |
Cancer letters |
Medium |
27566398
|
| 2022 |
TUFT1 is SUMOylated at lysine 79 by the E3 SUMO ligase TRIM27. TUFT1 binds TRIM27 through its N-terminus. SUMOylation-deficient TUFT1 (K79 mutant) fails to activate AKT/mTOR signaling and impairs gastric cancer cell proliferation, migration, and invasion. SUMOylated TUFT1 also forms a complex with RABGAP1 to promote perinuclear accumulation of mTORC1. |
SUMOylation site mutagenesis, Co-IP, functional assays (proliferation, migration, invasion), western blot for AKT/mTOR phosphorylation, TRIM27 knockdown epistasis |
Cancer science |
Medium |
36380570
|
| 2019 |
TUFT1 promotes metastasis and chemoresistance in TNBC by activating Rab5 through binding to p85α, which leads to Tiam1 recruitment and subsequent Rac1 activation, with concurrent downregulation of NF-κB pathway and proapoptotic factors. |
Co-immunoprecipitation (TUFT1-p85α interaction), GTP activity assays (Rab5-GTP, Rac1-GTP), shRNA knockdown, nude mouse xenograft metastasis model, Transwell assays |
Cancer cell international |
Medium |
31572059
|
| 2019 |
TUFT1 promotes TNBC tumor cell metastasis and stemness by upregulating the Rac1/β-catenin pathway, and lack of TUFT1 sensitizes cells to chemotherapy via downregulation of this pathway. |
shRNA knockdown, GTP activity assays (Rac1-GTP), migration/invasion assays, sphere formation, apoptosis assay, nude mouse xenograft spontaneous lung metastasis model, western blot |
Frontiers in oncology |
Medium |
31338333
|
| 2020 |
BRD9 epigenetically upregulates TUFT1 expression by promoting binding of P300 acetyltransferase to the TUFT1 promoter and increasing H3K27Ac at the promoter, thereby activating AKT signaling in HCC cells. |
ChIP-qPCR (P300 and H3K27Ac at TUFT1 promoter), BRD9 knockdown/inhibition, TUFT1 rescue experiments, western blot for AKT phosphorylation |
Cell death & disease |
Medium |
32908135
|
| 2023 |
Biallelic loss-of-function TUFT1 variants cause woolly hair and superficial skin fragility. Tuftelin-1 is localized to peripheral cell membranes of keratinocytes in normal skin, and loss of TUFT1 leads to desmosomal detachment, acantholysis, widening of intercellular spaces throughout the epidermis, and perinuclear retraction of intermediate filaments. |
Whole-genome/exome sequencing, immunofluorescence microscopy (localization in normal vs. patient skin), transmission electron microscopy (desmosomal ultrastructure), haplotype analysis, single-cell RNA sequencing co-expression analysis |
The British journal of dermatology |
High |
36689522
|
| 2023 |
TUFT1 is a desmosome-associated protein whose location within the desmosome depends on the presence of the desmoplakin carboxy-terminal tail. Loss of TUFT1 causes acantholysis, perinuclear retraction of intermediate filaments, and reduced mechanical stress resistance in keratinocytes. A Tuft1-knockout mouse model recapitulates skin fragility, woolly hair, and palmoplantar keratoderma. |
Immunolabeling (desmosomal localization), transfection studies (desmoplakin carboxy-terminal tail dependence), Tuft1-knockout mouse model, keratinocyte mechanical stress assays, patient skin histology |
The Journal of investigative dermatology |
High |
37716648
|
| 2017 |
Overexpression of wild-type or mutant TUFT1 in ATDC5 chondrogenic cells inhibits chondrogenic differentiation (decreased marker gene expression, reduced cartilage nodule formation) in calcifying conditions. The T175M variant increases extracellular matrix calcium content and reduces proteoglycan content compared to wild-type TUFT1 overexpression. |
HEK293 cell transfection (mRNA/protein expression), ATDC5 overexpression in calcifying conditions, chondrogenic marker gene expression, cartilage nodule formation assay, calcium and proteoglycan content measurement |
PloS one |
Medium |
28410428
|
| 2018 |
Tuft1 promotes thyroid carcinoma cell invasion and proliferation and suppresses apoptosis through the Akt-mTOR and Akt-GSK3β signaling pathways. Addition of recombinant Tuft1 protein to TC cells increases phosphorylation of Akt, mTOR, and GSK3β; mTOR inhibitor abrogates Tuft1-induced invasion and proliferation, while GSK3β inhibitor abrogates Tuft1-induced proliferation only. |
shRNA knockdown, recombinant protein treatment, mTOR inhibitor (Dactolisib) and GSK3β inhibitor (CHIR-98014) pharmacological epistasis, western blot for pathway phosphorylation, in vivo xenograft |
American journal of translational research |
Medium |
30662679
|
| 2025 |
TUFT1 is a centrosomal protein that localizes to the proximal ends of parent centrioles. TUFT1 prevents centrosome amplification and mitotic spindle multipolarity by suppressing premature polo-like kinase 1 (PLK1) activation. TUFT1 is phosphorylated by NEK2 kinase, and the phosphorylation status of TUFT1 is essential for coordinating centrosome number and cell proliferation. |
Immunofluorescence (centrosomal localization), TUFT1 loss-of-function (centrosome number, spindle multipolarity readouts), PLK1 activity assays, NEK2-mediated phosphorylation assay, western blot, clinical breast cancer sample analysis |
Cell death & disease |
Medium |
41022752
|
| 2026 |
TUFT1 is a novel TGF-β receptor II (TβRII) binding protein in hepatic stellate cells (HSCs). TUFT1 interacts with TβRII via its N-terminal fragments (amino acids 1-86 and 87-157), protecting TβRII from lysosomal degradation by competing with caveolin-1 for TβRII binding, diverting TβRII from the lipid rafts/caveolae-mediated degradation pathway into the endosome-mediated trafficking and signaling pathway, thereby facilitating TGF-β signaling and myofibroblastic activation of HSCs. |
Immunoprecipitation coupled with mass spectrometry (TβRII-TUFT1 interaction discovery), Co-IP (domain mapping, caveolin-1 competition), lysosomal degradation assays, TUFT1 knockdown with TGF-β signaling readouts, in vivo HSC/CRC co-implantation and portal vein injection mouse models, bulk RNA sequencing |
Cell death and differentiation |
High |
41593321
|
| 2025 |
TUFT1 binds to ATF1 (activating transcription factor 1) in cervical cancer cells and positively regulates ATF1 expression. ATF1 overexpression counteracts the effects of TUFT1 silencing on proliferation, migration, invasion, stemness, and EGFR signaling. |
Co-IP assay (TUFT1-ATF1 interaction), RT-qPCR and western blot (ATF1 expression after TUFT1 silencing), epistasis rescue (co-transfection of TUFT1 siRNA + ATF1 overexpression), functional assays |
Cell biochemistry and biophysics |
Low |
39948288
|
| 2022 |
ATF2 transcription factor directly targets the miR-548p promoter (confirmed by ChIP and luciferase assay), and miR-548p directly binds the 3'-UTR of TUFT1 to suppress its expression, thereby suppressing PI3K/AKT signaling in HCC. |
Chromatin immunoprecipitation (ATF2 binding to miR-548p promoter), luciferase reporter assay (miR-548p binding to TUFT1 3'-UTR), western blot for PI3K/AKT signaling, functional assays |
Hepatology research |
Low |
34904343
|