Abstract:
:The heat shock protein 90 (Hsp90) has a critical role in malignant transformation. Whereas its ability to maintain the functional conformations of mutant and aberrant oncoproteins is established, a transformation-specific regulation of the antiapoptotic phenotype by Hsp90 is poorly understood. By using selective compounds, we have discovered that small-cell lung carcinoma is a distinctive cellular system in which apoptosis is mainly regulated by Hsp90. Unlike the well-characterized antiapoptotic chaperone Hsp70, Hsp90 is not a general inhibitor of apoptosis, but it assumes this role in systems such as small-cell lung carcinoma, in which apoptosis is uniquely dependent on and effected through the intrinsic pathway, without involvement of caspase elements upstream of mitochondria or alternate pathways that are not apoptosome-channeled. These results provide important evidence for a transformation-specific interplay between chaperones in regulating apoptosis in malignant cells.
journal_name
Nat Chem Bioljournal_title
Nature chemical biologyauthors
Rodina A,Vilenchik M,Moulick K,Aguirre J,Kim J,Chiang A,Litz J,Clement CC,Kang Y,She Y,Wu N,Felts S,Wipf P,Massague J,Jiang X,Brodsky JL,Krystal GW,Chiosis Gdoi
10.1038/nchembio.2007.10subject
Has Abstractpub_date
2007-08-01 00:00:00pages
498-507issue
8eissn
1552-4450issn
1552-4469pii
nchembio.2007.10journal_volume
3pub_type
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