Phosphorylation of the eukaryotic initiation factor 3f by cyclin-dependent kinase 11 during apoptosis

Shi, Jiaqi; Hershey, John W.B.; Nelson, Mark A.

doi:10.1016/j.febslet.2009.02.028

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Volume 583, Issue 6 , Pages 971-977, 18 March 2009

Phosphorylation of the eukaryotic initiation factor 3f by cyclin-dependent kinase 11 during apoptosis

Edited by Barry Halliwell

Jiaqi Shi
- Department of Surgery, Arizona Cancer Center, University of Arizona, 1501 N. Campbell Avenue AHSC Rm5233, Tucson, AZ 85724, USA
- Department of Pathology, University of Arizona, Tucson, AZ 85724, USA
- Corresponding authors. Address: Department of Surgery, Arizona Cancer Center, University of Arizona, 1501 N. Campbell Avenue AHSC Rm5233, Tucson, AZ 85724, USA. Fax: +1 520 6266898 (J. Shi), +1 520 6268410 (M.A. Nelson).
John W.B. Hershey
- Department of Biological Chemistry, School of Medicine, University of California, Davis, CA 95616, USA
Mark A. Nelson
- Department of Pathology, University of Arizona, Tucson, AZ 85724, USA
- Corresponding authors. Address: Department of Surgery, Arizona Cancer Center, University of Arizona, 1501 N. Campbell Avenue AHSC Rm5233, Tucson, AZ 85724, USA. Fax: +1 520 6266898 (J. Shi), +1 520 6268410 (M.A. Nelson).

Received 5 February 2009; received in revised form 13 February 2009; accepted 17 February 2009. published online 24 February 2009.

Abstract

eIF3f is a subunit of eukaryotic initiation factor 3 (eIF3). We previously showed that eIF3f is phosphorylated by cyclin dependent kinase 11 (CDK11^p46) which is an important effector in apoptosis. Here, we identified a second eIF3f phosphorylation site (Thr119) by CDK11^p46 during apoptosis. We demonstrated that eIF3f is directly phosphorylated by CDK11^p46 in vivo. Phosphorylation of eIF3f plays an important role in regulating its function in translation and apoptosis. Phosphorylation of eIF3f enhances the association of eIF3f with the core eIF3 subunits during apoptosis. Our data suggested that eIF3f may inhibit translation by increasing the binding to the eIF3 complex during apoptosis.

Structured summary

MINT-6948874: EIF3b (uniprotkb:P55884) physically interacts (MI:0218) with EIF3f (uniprotkb:O00303) by anti bait coimmunoprecipitation (MI:0006)

MINT-6948891: EIF3b (uniprotkb:P55884) physically interacts (MI:0218) with EIF3c (uniprotkb:Q99613), EIF3a (uniprotkb:Q14152) and EIF3f (uniprotkb:O00303) by anti bait coimmunoprecipitation (MI:0006)

MINT-6948836, MINT-6948849, MINT-6948862: CDK11p46 (uniprotkb:P21127) phosphorylates (MI:0217) EIF3f (uniprotkb:O00303) by protein kinase assay (MI:0424)

Abbreviations: CDK11, cyclin dependent kinase 11, eIF3, eukaryotic initiation factor 3, GAPDH, glyceraldehydes-3-phosphate dehydrogenase, GST, glutathione S-transferase, MS, mass spectrometry, m/z, mass to charge ratio