title: Chaperones in cell cycle regulation and mitogenic signal transduction: a review.
abstract: Chaperones/heat shock proteins (HSPs) of the HSP90 and HSP70 families show elevated levels in proliferating mammalian cells and a cell cycle-dependent expression. They transiently associate with key molecules of the cell cycle control system such as Cdk4, Wee-1, pRb, p53, p27/Kip1 and are involved in the nuclear localization of regulatory proteins. They also associate with viral oncoproteins such as SV40 super T, large T and small t antigen, polyoma large and middle S antigen and EpsteinBarr virus nuclear antigen. This association is based on a J-domain in the viral proteins and may assist their targeting to the pRb/E2F complex. Small HSPs and their state of phosphorylation and oligomerization also seem to be involved in proliferation and differentiation. Chaperones/HSPs thus play important roles within cell cycle processes. Their exact functioning, however, is still a matter of discussion. HSP90 in particular, but also HSP70 and other chaperones associate with proteins of the mitogen-activated signal cascade, particularly with the Src kinase, with tyrosine receptor kinases, with Raf and the MAP-kinase activating kinase (MEK). This apparently serves the folding and translocation of these proteins, but possibly also the formation of large immobilized complexes of signal transducing molecules (scaffolding function).
authors: Institute of Cell Biology, Biochemistry and Biotechnology, University of Bremen, Germany.
authors: K
authors: K
authors: Helmbrecht
authors: E
authors: E
authors: Zeise
authors: L
authors: L
authors: Rensing
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000502:physiology*; D018840:HSP70 Heat-Shock Proteins / Q000502:physiology; D018841:HSP90 Heat-Shock Proteins / Q000502:physiology; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D018832:Molecular Chaperones / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D018832:Molecular Chaperones; D020928:Mitogen-Activated Protein Kinases