Gene interactions and pathways from curated databases and text-mining
Proc Natl Acad Sci U S A 2008, PMID: 19064921

Tcl1 functions as a transcriptional regulator and is directly involved in the pathogenesis of CLL.

Pekarsky, Yuri; Palamarchuk, Alexey; Maximov, Vadim; Efanov, Alexey; Nazaryan, Natalya; Santanam, Urmila; Rassenti, Laura; Kipps, Thomas; Croce, Carlo M

B cell chronic lymphocytic leukemia (B-CLL) is the most common human leukemia. Deregulation of the T cell leukemia/lymphoma 1 (TCL1) oncogene in mouse B cells causes a CD5-positive leukemia similar to aggressive human B-CLLs. To examine the mechanisms by which Tcl1 protein exerts oncogenic activity in B cells, we investigated the effect of Tcl1 expression on NF-kappaB and activator protein 1 (AP-1) activity. We found that Tcl1 physically interacts with c-Jun, JunB, and c-Fos and inhibits AP-1 transcriptional activity. Additionally, Tcl1 activates NF-kappaB by physically interacting with p300/CREB binding protein. We then sequenced the TCL1 gene in 600 B-CLL samples and found 2 heterozygous mutations: T38I and R52H. Importantly, both mutants showed gain of function as AP-1 inhibitors. The results indicate that Tcl1 overexpression causes B-CLL by directly enhancing NF-kappaB activity and inhibiting AP-1.

Diseases/Pathways annotated by Medline MESH: Leukemia, Lymphocytic, Chronic, B-Cell
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Text Mining Data

activator protein 1 (AP-1) — Tcl1: " To examine the mechanisms by which Tcl1 protein exerts oncogenic activity in B cells, we investigated the effect of Tcl1 expression on NF-kappaB and activator protein 1 (AP-1) activity "

NF-kappaB — Tcl1: " To examine the mechanisms by which Tcl1 protein exerts oncogenic activity in B cells, we investigated the effect of Tcl1 expression on NF-kappaB and activator protein 1 (AP-1) activity "

AP-1 ⊣ Tcl1: " We found that Tcl1 physically interacts with c-Jun, JunB, and c-Fos and inhibits AP-1 transcriptional activity "

NF-kappaB → Tcl1: " Additionally, Tcl1 activates NF-kappaB by physically interacting with p300/CREB binding protein "

AP-1 ⊣ NF-kappaB: " The results indicate that Tcl1 overexpression causes B-CLL by directly enhancing NF-kappaB activity and inhibiting AP-1 "

Manually curated Databases

  • IRef Biogrid Interaction: TCL1A — JUNB (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: TCL1A — JUN (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: FOS — TCL1A (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: EP300 — FOS (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: EP300 — TCL1A (physical association, affinity chromatography technology)
In total, 5 gene pairs are associated to this article in curated databases