The IB kinase (IKK) holocomplex, containing the kinases IKK␣, IKK␤, and the scaffold NEMO (NF-B essential modifier), mediates activation of NF-B by numerous physiological stimuli. Heat shock protein 90 (Hsp90) and the co-chaperone Cdc37 have been indicated as additional subunits, but their specific functions in signal transduction are indistinct. Using an RNA interference approach, we demonstrate that Cdc37 recruits Hsp90 to the IKK complex in a transitory manner, preferentially via IKK␣. Binding is conferred by N-terminal as well as C-terminal residues of Cdc37. Cdc37 is essential for the maturation of de novo synthesized IKKs into enzymatically competent kinases but not for assembly of an IKK holocomplex. Mature IKKs, T-loop-phosphorylated after stimulation either by receptor-mediated signaling or upon DNA damage, further require Hsp90-Cdc37 to generate an activated state. Thus, the present data denote Hsp90-Cdc37 as a transiently acting essential regulatory component of IKK signaling.NF-B maintains key functions in various biological and pathological processes, including immune and inflammatory reactions, development, proliferation, apoptosis, stress responses, and oncogenesis (1-3). Three major NF-B-activating pathways can be distinguished. In the first, canonical pathway, a broad range of extracellular stimuli, including bacterial pathogens, antigens, mitogens, and inflammatory cytokines, induce diverse intracellular cascades, which activate the IB kinase (IKK) 4 complex. IKK-mediated phosphorylation triggers IB and p105 polyubiquitination by the SCF ␤TrCP E3 ligase complex and subsequent proteasomal destruction, resulting in the release of p50-, p65-, and c-Rel-containing heterodimers (1, 4). With much slower kinetics, a second, noncanonical NF-B pathway induces C-terminal processing of NF-B2/p100 to generate p52-containing complexes (5). Finally, a "nuclear-tocytoplasmic" pathway promotes NF-B activation in response to DNA damage (6).The IKK complex has a large apparent molecular mass of 700 -900 kDa and contains the kinases IKK␣ and IKK␤ as well as the regulatory nonenzymatic scaffold protein IKK␥, also known as NEMO (NF-B essential modifier) (1, 7). Stoichiometric analyses indicated equimolar content of IKK␥ and kinase molecules (8, 9) in the IKK complex, where a tetramer of IKK␥ is thought to bind to two kinase dimers (10). The scaffold protein ELKS has been proposed as a further regulatory component of cellular IKK complexes (11). IKK activation is dependent on phosphorylation at activation loop (T-loop) serines, either by upstream IKK kinases or by autophosphorylation. The activation process involves catalytic, nondestructive Lys-63-linked polyubiquitination (Ub K63 ) of IKK␥ as well as Ub K63 binding by IKK␥ (12, 13). Moreover, conformational changes by induced protein interactions may also be a mechanism to stimulate IKK activity. A number of regulatory proteins have been suggested to interact with IKK components (reviewed in Refs. 1 and 7). Among them, the chaperones Hsp90 and Cdc37 were proposed ...

Photoinduced nucleation of mercury vapor is studied experimentally in an upward thermal diffusion cloud chamber. The rate of nucleation is greatly increased when the supersaturated vapor is illuminated with light absorbed by the vapor molecules. In analogy to ion-induced nucleation the photoinduced nucleation can be explained as a general effect for all condensing atoms or molecules forming long living electronically excited states.

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