NF-B activation is a critical component in the transcriptional response to hypoxia. However, the underlying mechanisms that control its activity under these conditions are unknown. Here we report that under hypoxic conditions, IB kinase (IKK) activity is induced through a calcium/calmodulin-dependent kinase 2 (CaMK2)-dependent pathway distinct from that for other common inducers of NF-B. This process still requires IKK and the IKK kinase TAK1, like that for inflammatory inducers of NF-B, but the TAK1-associated proteins TAB1 and TAB2 are not essential. IKK complex activation following hypoxia requires Ubc13 but not the recently identified LUBAC (linear ubiquitin chain assembly complex) ubiquitin conjugation system. In contrast to the action of other NF-B inducers, IKK-mediated phosphorylation of IB␣ does not result in its degradation. We show that this results from IB␣ sumoylation by Sumo-2/3 on critical lysine residues, normally required for K-48-linked polyubiquitination. Furthermore, inhibition of specific Sumo proteases is sufficient to release RelA from IB␣ and activate NF-B target genes. These results define a novel pathway regulating NF-B activation, important to its physiological role in human health and disease.

First discovered in San Francisco Bay in 1992, the Chinese mitten crab, Eriocheir sinensis, has become established over hundreds of km 2 of the San Francisco Estuary. Ecological and economic impacts of this invasive species motivated our search for a greater understanding of the crab's life history as an important step in better management and control. Data for this life history model comes from the authors' research and scientific literature. Juvenile crabs migrate from the Estuary into fresh water where they develop into adults. Environmental signals may stimulate gonad development that is followed by a downstream migration beginning at the end of summer. Mating occurs after the crabs reach saline water. Embryos are carried until hatching, and the larvae undergo five zoeal stages before settlement. Our model projects rates of development at various temperatures and growth increments, supports a minimum of 2 years in low salinity or freshwater habitat, and predicts that most California mitten crabs are at least 3 years old before becoming sexually mature. Environmental factors strongly influence the timing and duration of the crab's life stages, and are discussed in the context of a gradient of development times for worldwide populations of this important invasive species.

No abstract