ArticleMolecular cell2021
The IMiD target CRBN determines HSP90 activity toward transmembrane proteins essential in multiple myeloma.
Article in Molecular cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 61 citations in OpenAlex.
- Activating RARβ to overcome immunomodulatory drug resistance in t(4;14) human myeloma.Leukemia · 2026Article
- Safety considerations for cereblon-recruiting targeted protein degraders.Nature reviews. Drug discovery · 2026Review
- FKBP8 connects the Hsp70-Hsp90 chaperone machinery to the folding of membrane proteins.Nature communications · 2026Article
- Label-free protein-structure-sensitive live-cell microscopy for patient-specific assessment of myeloma therapy.Nature biomedical engineering · 2026Article
- Genome agnostic, multi-level non-oncogene addiction-based systems pharmacology for rescuing metastatic relapsed/refractory neoplasias.Frontiers in pharmacology · 2026Review
- Epigenetic regulation of Cereblon in cancer: molecular mechanisms and clinical implications.Genes & genomics · 2025Article
- Design, synthesis and evaluation of pyrrolobenzodiazepine (PBD)-based PROTAC conjugates for the selective degradation of the NF-κB RelA/p65 subunit.RSC medicinal chemistry · 2025Article
- Targeting degradation of IKZF1 and IKZF3 through modulation of the E3 ligase substrates in the context of cellular therapies for multiple myeloma.Biomarker research · 2025Review
- Integrated in vivo functional screens and multiomics analyses identify α-2,3-sialylation as essential for melanoma maintenance.Science advances · 2025Article
- Novel immunotargets in multiple myeloma: biological relevance and therapeutic potential.Biomarker research · 2025Review
- Advances in the structures, mechanisms and targeting of molecular chaperones.Signal transduction and targeted therapy · 2025Review
- Therapeutic targets in diabetic peripheral neuropathy: heat shock proteins.Frontiers in endocrinology · 2025Review
- Leveraging a disulfidptosis-based signature to characterize heterogeneity and optimize treatment in multiple myeloma.Frontiers in immunology · 2025Article
- Recruitment of Ahsa1 to Hsp90 is regulated by a conserved peptide that inhibits ATPase stimulation.EMBO reports · 2024Article
- The CBEMBO molecular medicine · 2024Article
- The role of Aha1 in cancer and neurodegeneration.Frontiers in molecular neuroscience · 2024Review
- Function, mechanism and drug discovery of ubiquitin and ubiquitin-like modification with multiomics profiling for cancer therapy.Acta pharmaceutica Sinica. B · 2023Review
- Pan-cancer analysis reveals the prognostic and immunologic roles of cereblon and its significance for PROTAC design.Heliyon · 2023Article
- Genome-scale functional genomics identify genes preferentially essential for multiple myeloma cells compared to other neoplasias.Nature cancer · 2023Article
- Molecular Anatomy of the EML4-ALK Fusion Protein for the Development of Novel Anticancer Drugs.International journal of molecular sciences · 2023Review
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Authors and funding
22 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The complex architecture of transmembrane proteins requires quality control (QC) of folding, membrane positioning, and trafficking as prerequisites for cellular homeostasis and intercellular communication. However, it has remained unclear whether transmembrane protein-specific QC hubs exist. Here we identify cereblon (CRBN), the target of immunomodulatory drugs (IMiDs), as a co-chaperone that specifically determines chaperone activity of HSP90 toward transmembrane proteins by means of counteracting AHA1. This function is abrogated by IMiDs, which disrupt the interaction of CRBN with HSP90. Among the multiple transmembrane protein clients of CRBN-AHA1-HSP90 revealed by cell surface proteomics, we identify the amino acid transporter LAT1/CD98hc as a determinant of IMiD activity in multiple myeloma (MM) and present an Anticalin-based CD98hc radiopharmaceutical for MM radio-theranostics. These data establish the CRBN-AHA1-HSP90 axis in the biogenesis of transmembrane proteins, link IMiD activity to tumor metabolism, and nominate CD98hc and LAT1 as attractive diagnostic and therapeutic targets in MM.
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