ArticleAutophagy2026
RPS6KA3/RSK2-mediated phosphorylation of DRAM2 promotes lysosomal targeting and autophagic flux in melanoma.
Article in Autophagy, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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13 authors.
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Abstract
Macroautophagy/autophagy is a critical process for maintaining cellular homeostasis and has emerging implications in cancer biology. DRAM2 (DNA damage regulated autophagy modulator 2), a transmembrane protein enriched at lysosomal membranes, has been implicated in autophagy regulation; however, the upstream mechanisms governing its trafficking and function remain unclear. In this study, we identified RPS6KA3/RSK2, a stress-responsive kinase downstream of the MAPK pathway, as a novel upstream kinase of DRAM2. RPS6KA3/RSK2 interacted with and phosphorylated DRAM2 at Ser263 within its cytosolic tail. This phosphorylation was required for AP3D1/AP-3-dependent trafficking of DRAM2 to the late endosomal-lysosomal pathway, thereby facilitating autolysosome formation and sustaining autophagic flux. In contrast, the non-phosphorylatable DRAM2
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