Proto-oncogene TCL1: more than just a coactivator for Akt

Serine threonine kinase Akt, also called PKB (protein kinase B), plays a central role in regulating intracellular survival. Deregulation of this Akt signaling pathway underlies various human neoplastic diseases. Recently, the proto-oncogene TCL1 (T cell leukemia 1), with a previously unknown physiol...

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Bibliographic Details
Published in:The FASEB journal 2007-08, Vol.21 (10), p.2273-2284
Main Authors: Noguchi, Masayuki, Ropars, Virginie, Roumestand, Christian, Suizu, Futoshi
Format: Article
Language:English
Subjects:
Akt-PH domain
Amino Acid Sequence
Humans
isoform
Leukemia, Prolymphocytic - genetics
Models, Molecular
Molecular Sequence Data
Molecular Weight
Multigene Family
Protein Conformation
Protein Isoforms - genetics
protein kinase B
Proto-Oncogene Proteins - chemistry
Proto-Oncogene Proteins - genetics
Proto-Oncogene Proteins c-akt - genetics
Proto-Oncogene Proteins c-akt - metabolism
T cell leukemia 1
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Summary:Serine threonine kinase Akt, also called PKB (protein kinase B), plays a central role in regulating intracellular survival. Deregulation of this Akt signaling pathway underlies various human neoplastic diseases. Recently, the proto-oncogene TCL1 (T cell leukemia 1), with a previously unknown physiological function, was shown to interact with the Akt pleckstrin homology domain, enhancing Akt kinase activity; hence, it functions as an Akt kinase coactivator. In contrast to pathological conditions in which the TCL1 gene is highly activated in various human neoplasmic diseases, the physiological expression of TCL1 is tightly limited to early developmental cells as well as various developmental stages of immune cells. The NBRE (nerve growth factor-responsive element) of the proximal TCL1 promoter sequences can regulate the restricted physiological expression of TCL1 in a negative feedback mechanism. Further, based on the NMR structural studies of Akt-TCL1 protein complexes, an inhibitory peptide, "Akt-in," consisting of the βA strand of TCL1, has been identified and has therapeutic potential. This review article summarizes and discusses recent advances in the understanding of TCL1-Akt functional interaction in order to clarify the biological action of the proto-oncogene TCL1 family and the development avenues for a suppressive drug specific for Akt, a core intracellular survival regulator.--Noguchi, M., Ropars, V., Roumestand, C., Suizu, F. Proto-oncogene TCL1: more than just a coactivator for Akt.
ISSN:0892-6638
1530-6860
DOI:10.1096/fj.06-7684com