Interaction of Hsp90 with ribosomal proteins protects from ubiquitination and proteasome-dependent degradation.
Heat-shock protein 90 (Hsp90) is a molecular chaperone that plays a key role in the conformational maturation of various transcription factors and protein kinases in signal transduction. Multifunctional ribosomal protein S3 (rpS3), a component of the ribosomal small subunit, is involved in DNA repair and apoptosis. Our data show that Hsp90 binds directly to rpS3 and the functional consequence of Hsp90-rpS3 interaction results in the prevention of the ubiquitination and the proteasome-dependent degradation of rpS3, subsequently retaining the function and the biogenesis of the ribosome. Interference of Hsp90 activity by Hsp90 inhibitors appears to dissociate rpS3 from Hsp90, associate the protein with Hsp70, and induce the degradation of free forms of rpS3. Furthermore, ribosomal protein S6 (rpS6) also interacted with Hsp90 and exhibited a similar effect upon treatment with Hsp90 inhibitors. Therefore, we conclude that Hsp90 regulates the function of ribosomes by maintaining the stability of 40S ribosomal proteins such as rpS3 and rpS6.
Kim
Tae-Sung
TS
Laboratory of Biochemistry, School of Life Sciences and Biotechnology, and BioInstitute, Korea University, Seoul 136-701, South Korea.
Jang
Chang-Young
CY
Kim
Hag Dong
HD
Lee
Jae Yung
JY
Ahn
Byung-Yoon
BY
Kim
Joon
J
D016227:Benzoquinones; D002460:Cell Line; D003600:Cytosol / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000502:physiology; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000502:physiology; D047029:Lactams, Macrocyclic; D018613:Microscopy, Confocal; D046988:Proteasome Endopeptidase Complex / Q000502:physiology*; D011485:Protein Binding; D011809:Quinones / Q000494:pharmacology; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012269:Ribosomal Proteins / Q000235:genetics / Q000378:metabolism*; D012270:Ribosomes / Q000502:physiology; D025801:Ubiquitin / Q000378:metabolism*
D016227:Benzoquinones; D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D047029:Lactams, Macrocyclic; D011809:Quinones; D011993:Recombinant Fusion Proteins; D012269:Ribosomal Proteins; D025801:Ubiquitin; C044152:ribosomal protein S3; D046988:Proteasome Endopeptidase Complex; C001277:geldanamycin