ACAP3 is a GTPase-activating protein (GAP) selective for the small GTPase Arf6 that governs cell morphological dynamics in both neural development and epithelial cancers PMID:27330119. In neurons, ACAP3 drives neurite outgrowth by cycling Arf6 between its GTP- and GDP-bound states; loss of ACAP3 raises GTP-bound Arf6 and abolishes outgrowth, a defect rescued by wild-type but not GAP-inactive ACAP3 PMID:27330119, and the same GAP-dependent activity is required for cortical neuronal migration in vivo PMID:28919417. In cancer cells, ACAP3 acts as a tumour suppressor: in lung adenocarcinoma it inhibits EGFR signalling by impairing EGFR recycling and accelerating lysosome-mediated EGFR degradation in a GAP-activity-dependent manner, suppressing proliferation PMID:41520057, and in papillary thyroid carcinoma it suppresses viability, migration, and invasion while promoting apoptosis through modulation of AKT and p53 signalling PMID:39098591. ACAP3 expression is held down epigenetically, via Myc-driven DNA hypermethylation and deacetylation in lung adenocarcinoma PMID:41520057 and via HDAC2 in papillary thyroid carcinoma PMID:39098591.
| Year | Confidence | Finding | PMIDs | Journal |
|---|---|---|---|---|
| 2016 | High | ACAP3 functions as a GTPase-activating protein (GAP) specific to Arf6 in mouse hippocampal neurons. Knockdown of ACAP3 abrogated neurite outgrowth, which was rescued by wild-type ACAP3 but not by a GAP-inactive mutant. ACAP3 knockdown significantly increased GTP-bound Arf6 levels, confirming its role as an Arf6 GAP. Cycling between active and inactive forms of Arf6, regulated by ACAP3 together with a guanine-nucleotide-exchange factor, is required for neurite outgrowth. | PMID:27330119 | The Biochemical journal |
| 2017 | High | ACAP3 is required for neuronal migration in the developing mouse cerebral cortex in vivo. In utero knockdown of ACAP3 significantly impaired cortical neuron migration and the associated morphological changes; rescue with wild-type ACAP3 restored migration, but a GAP-inactive mutant did not, indicating the mechanism depends on Arf6 GAP activity. | PMID:28919417 | Biochemical and biophysical research communications |
| 2024 | Medium | HDAC2 negatively regulates ACAP3 expression in papillary thyroid carcinoma (PTC) cells. ACAP3 overexpression suppressed viability, proliferation, migration, and invasion, and promoted apoptosis of PTC cells, modulating AKT and p53 signalling (decreased p-AKT/AKT ratio, increased p-p53/p53 ratio, altered Bcl-2/Bax and E-cadherin/N-cadherin expression); HDAC2 overexpression reversed the tumour-suppressive effects of ACAP3. | PMID:39098591 | The international journal of biochemistry & cell biology |
| 2026 | Medium | Myc mediates epigenetic silencing of ACAP3 via DNA hypermethylation and deacetylation in lung adenocarcinoma (LUAD). ACAP3 inhibits EGFR signalling by impairing EGFR recycling and accelerating lysosome-mediated EGFR degradation in a GAP activity-dependent manner, thereby suppressing LUAD cell proliferation in vitro and in vivo. | PMID:41520057 | British journal of cancer |
| 2010 | Low | The intronic minisatellite UPS29 of the ACAP3 (CENTB5) gene possesses enhancer-like activity in neuronal-type cells (rat astrocytes) but not uniformly across cell types, as demonstrated by reporter gene (EGFP) transient transfection assays in HeLa, F9, and rat astrocyte cultures. | PMID:21105360 | Tsitologiia |