Send to

Choose Destination
See comment in PubMed Commons below
J Exp Med. 2008 Feb 18;205(2):465-77. doi: 10.1084/jem.20070725. Epub 2008 Feb 11.

Targeted inactivation of the COP9 signalosome impairs multiple stages of T cell development.

Author information

Vita-Salute San Raffaele University School of Medicine, 20132 Milano, Italy.


Genetic programs promoting cell cycle progression, DNA repair, and survival are coordinately induced in developing T cells and require rapid turnover of effector molecules. As the COP9 signalosome (CSN) has been placed at the crossroads of these programs in lower organisms, we addressed its role by conditionally deleting CSN5/JAB1, its catalytic subunit, in developing thymocytes. CSN5/JAB1(del/del) thymocytes show defective S phase progression and massive apoptosis at the double-negative (DN) 4-double-positive (DP) transition stage, which is paralleled by altered turnover of selected CSN-controlled substrates, including p53, IkappaB-alpha, and beta-catenin. Combined dysregulation of the p53 and NF-kappaB pathways affects thymocyte survival by altering the mRNA and protein levels of selected Bcl-2 family members. Genetic complementation analysis performed on p53(-/-), Bcl-xL/Bcl-2A1, or T cell receptor transgenic backgrounds indicates that CSN5/JAB1 acts at distinct developmental stages to coordinate proliferation, survival, and positive selection of thymocytes by controlling the induction of defined genetic programs acting downstream of CSN-regulated transcription factors.

[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Support Center