HDM2-binding Partners: Interaction with Translation Elongation Factor EF1alpha

Overview

Journal J Proteome Res

Publisher American Chemical Society

Specialty Biochemistry

Date 2007 Mar 22

PMID 17373842

Citations 13

Authors

Rebecca Frum

Scott A Busby

Mahesh Ramamoorthy

Sumitra Deb

Jeffrey Shabanowitz

Donald F Hunt

Swati P Deb

Affiliations

Soon will be listed here.

Abstract

To understand the cellular functions of HDM2, we attempted to identify novel HDM2-interacting proteins by proteomic analysis. Along with previously identified interactions with the ribosomal proteins, our analysis reveals interactions of HDM2 with the ribosomal translation elongation factor EF1alpha, 40S ribosomal protein S20, tubulins, glyceraldehyde 3-phosphate dehydrogenase, and a proteolysis-inducing factor dermicidin in the absence of tumor suppressor p53. Because a CTCL tumor antigen HD-CL-08 has high degree of homology with EF1alpha, we confirmed interaction of HDM2 with EF1alpha by immunoprecipitation and Western blot analysis in transformed as well as near normal diploid cells. Endogenous HDM2- EF1alpha complex was detected in cancer cells overexpressing HDM2, suggesting a possible role of this interaction in HDM2-mediated oncogenesis. Consistent with their interaction, colocalization of HDM2 and EF1alpha can be detected in the cytoplasm of normal or transformed cells. Amino acid residues 1-58 and 221-325 of HDM2 were found to be essential for its interaction with EF1alpha, suggesting that the interaction is independent of its other ribosomal interacting proteins L5, L11, and L23. Overexpression of HDM2 did not affect translation. Because EF1alpha has been implicated in DNA replication and severing of microtubules, interaction of HDM2 with EF1alpha may signify a p53-independent cell growth regulatory role of HDM2.

Citing Articles

EF1α-associated protein complexes affect dendritic spine plasticity by regulating microglial phagocytosis in Fmr1 knock-out mice.

Su P, Yan S, Chen K, Huang L, Wang L, Lee F Mol Psychiatry. 2024; 29(4):1099-1113.

PMID: 38212373 DOI: 10.1038/s41380-023-02396-2.

Biochemical and clinical effects of RPS20 expression in renal clear cell carcinoma.

Shen C, Chen Z, Zhang Y, Xu W, Peng R, Jiang J Oncol Rep. 2022; 49(1).

PMID: 36484407 PMC: 9773015. DOI: 10.3892/or.2022.8459.

A novel 3'tRNA-derived fragment tRF-Val promotes proliferation and inhibits apoptosis by targeting EEF1A1 in gastric cancer.

Cui H, Li H, Wu H, Du F, Xie X, Zeng S Cell Death Dis. 2022; 13(5):471.

PMID: 35585048 PMC: 9117658. DOI: 10.1038/s41419-022-04930-6.

Interplay between human nucleolar GNL1 and RPS20 is critical to modulate cell proliferation.

Krishnan R, Boddapati N, Mahalingam S Sci Rep. 2018; 8(1):11421.

PMID: 30061673 PMC: 6065441. DOI: 10.1038/s41598-018-29802-y.

Loss of fragile X protein FMRP impairs homeostatic synaptic downscaling through tumor suppressor p53 and ubiquitin E3 ligase Nedd4-2.

Lee K, Jewett K, Chung H, Tsai N Hum Mol Genet. 2018; 27(16):2805-2816.

PMID: 29771335 PMC: 6454515. DOI: 10.1093/hmg/ddy189.

References

Martin S, Shabanowitz J, Hunt D, Marto J . Subfemtomole MS and MS/MS peptide sequence analysis using nano-HPLC micro-ESI fourier transform ion cyclotron resonance mass spectrometry. Anal Chem. 2000; 72(18):4266-74. DOI: 10.1021/ac000497v. View

Oliner J, Kinzler K, Meltzer P, GEORGE D, Vogelstein B . Amplification of a gene encoding a p53-associated protein in human sarcomas. Nature. 1992; 358(6381):80-3. DOI: 10.1038/358080a0. View

Jin A, Itahana K, Okeefe K, Zhang Y . Inhibition of HDM2 and activation of p53 by ribosomal protein L23. Mol Cell Biol. 2004; 24(17):7669-80. PMC: 506972. DOI: 10.1128/MCB.24.17.7669-7680.2004. View

Lozano G, Montes de Oca Luna R . MDM2 function. Biochim Biophys Acta. 1998; 1377(2):M55-9. DOI: 10.1016/s0304-419x(97)00037-1. View

Juven-Gershon T, Oren M . Mdm2: the ups and downs. Mol Med. 1999; 5(2):71-83. PMC: 2230410. View

Honda R, Yasuda H . Association of p19(ARF) with Mdm2 inhibits ubiquitin ligase activity of Mdm2 for tumor suppressor p53. EMBO J. 1999; 18(1):22-7. PMC: 1171098. DOI: 10.1093/emboj/18.1.22. View

Lohrum M, Ludwig R, Kubbutat M, Hanlon M, Vousden K . Regulation of HDM2 activity by the ribosomal protein L11. Cancer Cell. 2003; 3(6):577-87. DOI: 10.1016/s1535-6108(03)00134-x. View

Onel K, Cordon-Cardo C . MDM2 and prognosis. Mol Cancer Res. 2004; 2(1):1-8. View

Ganguli G, Wasylyk B . p53-independent functions of MDM2. Mol Cancer Res. 2004; 1(14):1027-35. View

10.

Zhao J, Bilsland A, Jackson K, Keith W . MDM2 negatively regulates the human telomerase RNA gene promoter. BMC Cancer. 2005; 5:6. PMC: 546012. DOI: 10.1186/1471-2407-5-6. View

11.

Ito A, Kawaguchi Y, Lai C, Kovacs J, Higashimoto Y, Appella E . MDM2-HDAC1-mediated deacetylation of p53 is required for its degradation. EMBO J. 2002; 21(22):6236-45. PMC: 137207. DOI: 10.1093/emboj/cdf616. View

12.

Kubbutat M, Jones S, Vousden K . Regulation of p53 stability by Mdm2. Nature. 1997; 387(6630):299-303. DOI: 10.1038/387299a0. View

13.

Haupt Y, Maya R, Kazaz A, Oren M . Mdm2 promotes the rapid degradation of p53. Nature. 1997; 387(6630):296-9. DOI: 10.1038/387296a0. View

14.

Shamovsky I, Ivannikov M, Kandel E, Gershon D, Nudler E . RNA-mediated response to heat shock in mammalian cells. Nature. 2006; 440(7083):556-60. DOI: 10.1038/nature04518. View

15.

Negrutskii B, Elskaya A . Eukaryotic translation elongation factor 1 alpha: structure, expression, functions, and possible role in aminoacyl-tRNA channeling. Prog Nucleic Acid Res Mol Biol. 1998; 60:47-78. DOI: 10.1016/s0079-6603(08)60889-2. View

16.

Finlay C . The mdm-2 oncogene can overcome wild-type p53 suppression of transformed cell growth. Mol Cell Biol. 1993; 13(1):301-6. PMC: 358909. DOI: 10.1128/mcb.13.1.301-306.1993. View

17.

Leng P, Brown D, Shivakumar C, Deb S, Deb S . N-terminal 130 amino acids of MDM2 are sufficient to inhibit p53-mediated transcriptional activation. Oncogene. 1995; 10(7):1275-82. View

18.

Honda R, Tanaka H, Yasuda H . Oncoprotein MDM2 is a ubiquitin ligase E3 for tumor suppressor p53. FEBS Lett. 1998; 420(1):25-7. DOI: 10.1016/s0014-5793(97)01480-4. View

19.

Oliner J, Pietenpol J, Thiagalingam S, Gyuris J, Kinzler K, Vogelstein B . Oncoprotein MDM2 conceals the activation domain of tumour suppressor p53. Nature. 1993; 362(6423):857-60. DOI: 10.1038/362857a0. View

20.

Minsky N, Oren M . The RING domain of Mdm2 mediates histone ubiquitylation and transcriptional repression. Mol Cell. 2004; 16(4):631-9. DOI: 10.1016/j.molcel.2004.10.016. View