AAMDC is an oncogenic signaling regulator amplified in estrogen receptor-positive breast cancer that drives estrogen-independent tumor growth by activating the PI3K-AKT-mTOR axis PMID:33772001. Downstream of this signaling, AAMDC controls the translational upregulation of ATF4 and MYC and the transcriptional output of AAMDC-dependent promoters, and ectopic AAMDC expression is sufficient to activate AKT PMID:33772001. Through these effectors AAMDC reprograms cellular metabolism, governing the expression of enzymes in the one-carbon folate, methionine, and lipid metabolism pathways PMID:33772001. AAMDC physically interacts with the Rab GTPase-activating protein RabGAP1L and colocalizes with RabGAP1L and Rab7a at endolysosomes, forming an assembly platform that links it to the endolysosomal compartment PMID:33772001. Beyond these findings, the biochemical activity of AAMDC itself and the structural basis of its signaling and RabGAP1L interaction have not been characterized in the available corpus.
| Year | Confidence | Finding | PMIDs | Journal |
|---|---|---|---|---|
| 2021 | Medium | AAMDC regulates PI3K-AKT-mTOR signaling, controlling the translational regulation of ATF4 and MYC, and modulating the transcriptional activity of AAMDC-dependent promoters; ectopic AAMDC expression is sufficient to activate AKT signaling, resulting in estrogen-independent tumor growth in estrogen receptor-positive breast cancer models. | PMID:33772001 | Nature communications |
| 2021 | Medium | AAMDC regulates the expression of metabolic enzymes involved in the one-carbon folate and methionine cycles and lipid metabolism in estrogen receptor-positive breast cancer cells. | PMID:33772001 | Nature communications |
| 2021 | Medium | AAMDC physically interacts with the RabGTPase-activating protein RabGAP1L, and AAMDC, RabGAP1L, and Rab7a colocalize in endolysosomes, forming an assembly platform. | PMID:33772001 | Nature communications |
| 2023 | Low | AAMDC promotes autophagy in gastric cancer cells through the AAMDC/MYC/ATF4/Sesn2 signaling pathway; overexpression of AAMDC reversed the inhibitory effect of solanine on autophagy, placing AAMDC upstream of MYC, ATF4, and Sesn2 in this pathway. | PMID:36789094 | Drug design, development and therapy |