{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T02:16:20Z","timestamp":1779329780114,"version":"3.51.4"},"reference-count":52,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2023,4,10]],"date-time":"2023-04-10T00:00:00Z","timestamp":1681084800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Qatar Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The Saccharomyces cerevisiae Agp2 is a plasma membrane protein initially reported to be an uptake transporter for L-carnitine. Agp2 was later rediscovered, together with three additional proteins, Sky1, Ptk2, and Brp1, to be involved in the uptake of the polyamine analogue bleomycin-A5, an anticancer drug. Mutants lacking either Agp2, Sky1, Ptk2, or Brp1 are extremely resistant to polyamines and bleomycin-A5, suggesting that these four proteins act in the same transport pathway. We previously demonstrated that pretreating cells with the protein synthesis inhibitor cycloheximide (CHX) blocked the uptake of fluorescently labelled bleomycin (F-BLM), raising the possibility that CHX could either compete for F-BLM uptake or alter the transport function of Agp2. Herein, we showed that the agp2\u0394 mutant displayed striking resistance to CHX as compared to the parent, suggesting that Agp2 is required to mediate the physiological effect of CHX. We examined the fate of Agp2 as a GFP tag protein in response to CHX and observed that the drug triggered the disappearance of Agp2 in a concentration- and time-dependent manner. Immunoprecipitation analysis revealed that Agp2-GFP exists in higher molecular weight forms that were ubiquitinylated, which rapidly disappeared within 10 min of treatment with CHX. CHX did not trigger any significant loss of Agp2-GFP in the absence of the Brp1 protein; however, the role of Brp1 in this process remains elusive. We propose that Agp2 is degraded upon sensing CHX to downregulate further uptake of the drug and discuss the potential function of Brp1 in the degradation process.<\/jats:p>","DOI":"10.3390\/ijms24086975","type":"journal-article","created":{"date-parts":[[2023,4,10]],"date-time":"2023-04-10T03:49:29Z","timestamp":1681098569000},"page":"6975","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["The Yeast Permease Agp2 Senses Cycloheximide and Undergoes Degradation That Requires the Small Protein Brp1-Cellular Fate of Agp2 in Response to Cycloheximide"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6375-2566","authenticated-orcid":false,"given":"Ashima","family":"Mohanty","sequence":"first","affiliation":[{"name":"Division of Genomics and Precision Medicine, College of Health and Life Sciences, Hamad Bin Khalifa University, Education City, Qatar Foundation, Doha P.O. Box 34110, Qatar"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abdallah","family":"Alhaj Sulaiman","sequence":"additional","affiliation":[{"name":"Division of Biological and Biomedical Sciences, College of Health and Life Sciences, Hamad Bin Khalifa University, Education City, Qatar Foundation, Doha P.O. Box 34110, Qatar"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1140-883X","authenticated-orcid":false,"given":"Balasubramanian","family":"Moovarkumudalvan","sequence":"additional","affiliation":[{"name":"Division of Genomics and Precision Medicine, College of Health and Life Sciences, Hamad Bin Khalifa University, Education City, Qatar Foundation, Doha P.O. Box 34110, Qatar"},{"name":"Division of Biological and Biomedical Sciences, College of Health and Life Sciences, Hamad Bin Khalifa University, Education City, Qatar Foundation, Doha P.O. Box 34110, Qatar"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Reem","family":"Ali","sequence":"additional","affiliation":[{"name":"Division of Biological and Biomedical Sciences, College of Health and Life Sciences, Hamad Bin Khalifa University, Education City, Qatar Foundation, Doha P.O. Box 34110, Qatar"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7945-5320","authenticated-orcid":false,"given":"Mustapha","family":"Aouida","sequence":"additional","affiliation":[{"name":"Division of Biological and Biomedical Sciences, College of Health and Life Sciences, Hamad Bin Khalifa University, Education City, Qatar Foundation, Doha P.O. Box 34110, Qatar"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dindial","family":"Ramotar","sequence":"additional","affiliation":[{"name":"Division of Biological and Biomedical Sciences, College of Health and Life Sciences, Hamad Bin Khalifa University, Education City, Qatar Foundation, Doha P.O. 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