The TCL1 oncoprotein binds the RNase PH domains of the PNPase exoribonuclease without affecting its RNA degrading activity

French, Samuel W.; Dawson, David W.; Chen, Hsiao-Wen; Rainey, Robert N.; Sievers, Stuart A.; Balatoni, Cynthia E.; Wong, Larry; Troke, Joshua J.; Nguyen, Mai T.N.; Koehler, Carla M.; Teitell, Michael A.

doi:10.1016/j.canlet.2006.07.006

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Volume 248, Issue 2 , Pages 198-210, 18 April 2007

The TCL1 oncoprotein binds the RNase PH domains of the PNPase exoribonuclease without affecting its RNA degrading activity

Samuel W. French
- Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-1732, USA
David W. Dawson
- Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-1732, USA
Hsiao-Wen Chen
- Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-1732, USA
Robert N. Rainey
- Department of Chemistry and Biochemistry, UCLA, Los Angeles, CA 90095-1569, USA
Stuart A. Sievers
- Department of Chemistry and Biochemistry, UCLA, Los Angeles, CA 90095-1569, USA
Cynthia E. Balatoni
- Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-1732, USA
Larry Wong
- Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-1732, USA
Joshua J. Troke
- Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-1732, USA
Mai T.N. Nguyen
- Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-1732, USA
Carla M. Koehler
- Department of Chemistry and Biochemistry, UCLA, Los Angeles, CA 90095-1569, USA
- Molecular Biology Institute and Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, CA 90095, USA
Michael A. Teitell
- Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-1732, USA
- Molecular Biology Institute and Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, CA 90095, USA
- Corresponding author. Tel.: +1 310 206 6754; fax: +1 310 267 0382.

Received 12 April 2006; accepted 13 July 2006.

Abstract

TCL1 is an AKT kinase coactivator that, when dysregulated, initiates mature lymphocyte malignancies in humans and transgenic mice. While TCL1 augments AKT pathway signaling, additional TCL1 interacting proteins that may contribute to cellular homeostasis or transformation are lacking. Here, an exoribonuclease, PNPase, was identified in a complex with TCL1. The AKT interaction domain on TCL1 bound either RNase PH repeat domain of PNPase without influencing its RNA degrading activity, which was compatible with predicted docking models for a TCL1–PNPase complex. Our data provide a novel protein interaction for mammalian PNPase that may impact TCL1 mediated transformation.

Keywords: TCL1, PNPase, Exoribonuclease, Mass spectrometry, Leukemia, Lymphoma