1: Immunity. 2002 Jan;16(1):9-21. 

Helix-loop-helix proteins regulate pre-TCR and TCR signaling through modulation
of Rel/NF-kappaB activities.

Kim D, Xu M, Nie L, Peng XC, Jimi E, Voll RE, Nguyen T, Ghosh S, Sun XH.

Immunobiology and Cancer Program, Oklahoma Medical Research Foundation, 825 NE
13th Street, Oklahoma City, OK 73104, USA.

E2A and HEB are basic helix-loop-helix transcription factors essential for T
cell development. Complete inhibition of their activities through transgenic
overexpression of their inhibitors Id1 and Tal1 leads to a dramatic loss of
thymocytes. Here, we suggest that bHLH proteins play important roles in
establishing thresholds for pre-TCR and TCR signaling. Inhibition of their
function allows double-negative cells to differentiate without a functional
pre-TCR, while anti-CD3 stimulation downregulates bHLH activities. We also find
that the transcription factor NF-kappaB becomes activated in transgenic
thymocytes. Further activation of NF-kappaB exacerbates the loss of thymocytes,
whereas inhibition of NF-kappaB leads to the rescue of double-positive
thymocytes. Therefore, we propose that E2A and HEB negatively regulate pre-TCR
and TCR signaling and their removal causes hyperactivation and apoptosis of
thymocytes.

PMID: 11825562 [PubMed - indexed for MEDLINE]


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