RIP1-mediated regulation of lymphocyte survival and death responses.
RIP1 is an adaptor serine/threonine kinase associated with the signaling complex of death receptors (DRs) including Fas, TNFR1, and TRAIL-Rs which can initiate apoptosis. While DRs are dispensable throughout development, RIP1 deletion results in perinatal lethality. The developmental defect caused by absence of RIP1 remains unexplained. In previous studies, RIP1-deficient hematopoietic progenitors failed to reconstitute the T cell compartment and our recent data indicate a new role for RIP1 in TCR-induced activation of the pro-survival NF-κB pathway. Here, we show that RIP1 is also critical for B cell development. In addition, RIP1(-/-) B cells stimulated through LPS/TLR4 are impaired in NF-κB activation but have no major defect in the Akt pathway. Recently, RIP1 has also emerged as a critical player in necrosis-like death, necroptosis, in various cell lines. We have demonstrated that RIP1 deficiency can reverse the embryonic and T cell proliferation defects in mice lacking FADD, a caspase adaptor protein, which indicates a potential role for RIP1 in mediating in vivo necroptosis. We provide an overview and discussion of the accumulating data revealing insights into the diverse functions of RIP1 in survival and death signaling in lymphocytes.
Department of Microbiology and Immunology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA. jzhang@mail.jci.tju.edu
Jianke
J
Zhang
Haibing
H
Zhang
Jinghe
J
Li
Stephen
S
Rosenberg
Emily C
EC
Zhang
Xiaohui
X
Zhou
Fengsong
F
Qin
Mathew
M
Farabaugh
D000818:Animals; D002470:Cell Survival / Q000235:genetics; D053200:Fas-Associated Death Domain Protein / Q000235:genetics / Q000276:immunology*; D020690:GTPase-Activating Proteins / Q000235:genetics / Q000276:immunology*; D006801:Humans; D008214:Lymphocytes / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D016328:NF-kappa B / Q000276:immunology; D009336:Necrosis / Q000235:genetics / Q000276:immunology*; D051057:Proto-Oncogene Proteins c-akt / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology
C505534:Fadd protein, mouse; D053200:Fas-Associated Death Domain Protein; D020690:GTPase-Activating Proteins; D016328:NF-kappa B; C490620:Ralbp1 protein, mouse; D051057:Proto-Oncogene Proteins c-akt