| 2018 |
FRMD8 (iTAP) is a component of the iRhom2/ADAM17 sheddase complex, binding directly to the cytoplasmic N-terminus of iRhom proteins; it is necessary to stabilise iRhom2 and ADAM17 at the cell surface, and in its absence iRhom2 and ADAM17 are degraded via the endolysosomal pathway, resulting in reduced ADAM17-mediated shedding of TNFα and EGF receptor ligands. |
Co-immunoprecipitation/mass spectrometry screen, reciprocal Co-IP, genetic knockdown/knockout in iPSC-derived human macrophages and mouse tissues, cell-surface stability assays, endolysosomal pathway inhibition experiments |
eLife |
High |
29897333 29897336
|
| 2018 |
FRMD8/iTAP binds to iRhom proteins and enhances their cell-surface stability, preventing degradation of iRhom and TACE (ADAM17) in lysosomes; depletion of iTAP in primary human macrophages profoundly impaired TNF production, and tissues from iTAP KO mice show pronounced depletion of active TACE levels. |
Immunoprecipitation/mass spectrometry, siRNA knockdown in primary human macrophages, iTAP KO mouse tissue analysis, lysosomal degradation assays |
eLife |
High |
29897333
|
| 2023 |
iTAP/FRMD8 KO mice exhibit defects in inflammatory responses and intestinal epithelial barrier repair; iTAP/FRMD8 also regulates cancer cell growth in a cell-autonomous manner and by modulating the tumor microenvironment, consistent with its role in controlling ADAM17 sheddase complex stability. |
iTAP/Frmd8 KO mouse phenotyping, in vivo tumor growth assays, inflammatory challenge experiments |
Life science alliance |
Medium |
36720499
|
| 2023 |
FRMD8 interacts separately with CDK7 and CDK4, disrupts the CDK7–CDK4 interaction to inhibit CDK4 activation, and competes with MDM2 to bind RB, thereby attenuating MDM2-mediated RB degradation and causing cell-cycle arrest. Frmd8 deficiency in mice accelerates colorectal adenoma formation. |
Co-immunoprecipitation, competitive binding assays, CDK4 activation assays, RB stability assays with MDM2, Frmd8 KO mouse AOM/DSS colorectal cancer model, peptide competition experiments |
Cell reports |
Medium |
37527040
|
| 2025 |
FRMD8 interacts with both ERα and UBE3A (an E3 ubiquitin ligase), and disrupts the UBE3A–ERα interaction, thereby blocking UBE3A-mediated ERα degradation; FRMD8 deficiency also suppresses ESR1 transcription via downregulation of FOXO3A, a transcription factor for ESR1. |
Co-immunoprecipitation, competitive binding assays, ERα protein stability assays, gene expression analysis, MMTV-Cre; Frmd8; PyMT mouse model, single-cell RNA profiling |
eLife |
Medium |
40213945
|
| 2025 |
In BRCA1-mutant TNBC cells, low FRMD8 expression inhibits cleavage of transmembrane TNF-α (tmTNF-α) and promotes surface tmTNF-α expression by failing to prevent iRhom2 degradation through the endocytic pathway, thereby promoting metastasis. |
Library screening, cellular functional assays, in vivo metastasis animal experiments, iRhom2 degradation assays, pharmacological rescue with paclitaxel and etanercept |
Cellular & molecular biology letters |
Medium |
40619383
|
| 2026 |
MALAT1 recruits PRC2 (Polycomb Repressive Complex 2) to transcriptionally repress FRMD8; MALAT1 knockdown upregulates FRMD8, which stabilises ADAM17 and enhances its proteolytic activity. RNA pull-down, RIP, and ChIP-PCR assays established the MALAT1–PRC2–FRMD8–ADAM17 regulatory axis in trophoblast cells. |
RNA pull-down, RNA immunoprecipitation (RIP), ChIP-PCR, MALAT1 knockdown, pharmacological ADAM17 inhibition, EZH2 inhibition |
European journal of cell biology |
Medium |
41985336
|