Small glutamine-rich protein/viral protein U-binding protein is a novel cochaperone that affects heat shock protein 70 activity

Peter C Angeletti, Doriann Walker, Antonito T. Panganiban

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

Molecular chaperone complexes containing heat shock protein (Hsp) 70 and Hsp90 are regulated by cochaperones, including a subclass of regulators, such as Hsp70 interacting protein (Hip), C-terminus of Hsp70 interacting protein (CHIP), and Hsp70-Hsp90 organizing factor (Hop), that contain tetratricopeptide repeats (TPRs), where Hsp70 refers to Hsp70 and its nearly identical constitutive counterpart, Hsc70, together. These proteins interact with the Hsp70 to regulate adenosine triphosphatase (ATPase) and folding activities or to generate the chaperone complex. Here we provide evidence that small glutamine-rich protein/viral protein U-binding protein (SGT/UBP) is a cochaperone that negatively regulates Hsp70. By "Far-Western" and pull-down assays, SGT/UBP was shown to interact directly with Hsp70 and weakly with Hsp90. The interaction of SGT/UBP with both these protein chaperones was mapped to 3 TPRs in SGT/UBP (amino acids 95-195) that are flanked by charged residues. Moreover, SGT/UBP caused an approximately 30% reduction in both the intrinsic ATPase activity of Hsc70 and the ability of Hsc70 to refold denatured luciferase in vitro. This negative effect of SGT/UBP on Hsc70 is similar in magnitude to that observed for the cochaperone CHIP. A role for SGT/UBP in protein folding is also supported by evidence that a yeast strain containing a deletion in the yeast homolog to SGT/UBP (ΔSGT/UBP) displays a 50-fold reduction in recovery from heat shock compared with the wild type parent. Together, these results are consistent with a regulatory role for SGT/UBP in the chaperone complex.

Original languageEnglish (US)
Pages (from-to)258-268
Number of pages11
JournalCell Stress and Chaperones
Volume7
Issue number3
DOIs
StatePublished - Jul 1 2002

Fingerprint

HSP70 Heat-Shock Proteins
Viral Proteins
Glutamine
Protein Binding
Carrier Proteins
Proteins
Yeast
Adenosine Triphosphatases
Protein folding
Molecular Chaperones
Yeasts
Protein C
Luciferases
Humulus
Assays
Protein Folding
Amino Acids
Recovery
Shock

ASJC Scopus subject areas

  • Clinical Biochemistry

Cite this

Small glutamine-rich protein/viral protein U-binding protein is a novel cochaperone that affects heat shock protein 70 activity. / Angeletti, Peter C; Walker, Doriann; Panganiban, Antonito T.

In: Cell Stress and Chaperones, Vol. 7, No. 3, 01.07.2002, p. 258-268.

Research output: Contribution to journalArticle

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