Birth pangs: the stressful origins of lymphocytes
J. Clin. Invest. Shiv Pillai, et al. 115:224 doi:10.1172/JCI24238 [
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Figure 1Multiple sensors initiate the UPR in vertebrates. IRE1α and PERK are integral-membrane ER kinases whose lumenal domains are triggered by misfolded proteins in the ER. IRE1α and its yeast homolog, IRE1, contain a lumenal stress-sensing domain (blue) as well as cytosolic kinase (magenta) and endoribonuclease (RNaseL, red) domains. ATF6 is another stress sensor, which is cleaved in response to stress to yield a fragment (green) that is transported to the nucleus. Both ATF6 and Blimp-1 (not shown) may contribute to the transcriptional induction of
XBP1. Very little is understood as to how IRE1α, a kinase that is activated by unfolded proteins in the ER, contributes to the induction of
Rag1,
Rag2, and
TdT to initiate and sustain V(D)J recombination during early B cell development.
