New role of human ribosomal protein S3: regulation of cell cycle via phosphorylation by cyclin‑dependent kinase 2

Han,Se Hee; Chung,Ji Hyung; Kim,Joon; Kim,Key‑Sun; Han,Ye Sun

doi:10.3892/ol.2017.5906

New role of human ribosomal protein S3: regulation of cell cycle via phosphorylation by cyclin‑dependent kinase 2

Authors:
- Se Hee Han
- Ji Hyung Chung
- Joon Kim
- Key‑Sun Kim
- Ye Sun Han
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Affiliations: Center for Diagnosis, Treatment and Care System of Dementia, Korea Institute of Science and Technology, Seoul 02792, Republic of Korea, Department of Applied Bioscience, College of Life Science, CHA University, Pocheon 11160, Republic of Korea, Laboratory of Biochemistry, Division of Life Sciences and Biotechnology, Korea University, Seoul 02841, Republic of Korea, Department of Advanced Technology Fusion, Konkuk University, Seoul 05029, Republic of Korea
Published online on: March 24, 2017 https://doi.org/10.3892/ol.2017.5906
Pages: 3681-3687
Copyright: © Han et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Human ribosomal protein S3 (hRpS3) is a component of the 40S ribosomal subunit that associated in protein synthesis. hRpS3 has additional ribosomal functions such as DNA repair, transcription, metastasis, and apoptosis via interaction with numerous signaling molecules and has different modifications. Cyclin‑dependent kinases (CDKs) are heterodimeric serine/threonine protein kinases that regulate cell cycle progression. Among its members, the Cdk1‑cyclin B complex is known to control cell progression in the G2/M phase, while Cdk2‑cyclin E/A complexes function in G1/S and S/G2 transition. In our previous study, we observed interaction between hRpS3 and Cdk1. The present study investigated the interaction between hRpS3 and Cdk2. Cdk2 phosphorylated hRps3 at amino acid residues S6 and T221 during the S‑phase. Furthermore, hRpS3 knockdown delayed cell cycle progression by modulating the expression of cell cycle‑related proteins, including cyclin B1 and cyclin E1. These findings suggest that hRpS3 is involved in Cdk2‑mediated cell cycle regulation.

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1	Gu Y, Rosenblatt J and Morgan DO: Cell cycle regulation of CDK2 activity by phosphorylation of Thr160 and Tyr15. EMBO J. 11:3995–4005. 1992.PubMed/NCBI
2	Aleem E, Kiyokawa H and Kaldis P: Cdc2-cyclin E complexes regulate the G1/S phase transition. Nat Cell Biol. 7:831–836. 2005. View Article : Google Scholar : PubMed/NCBI
3	Koff A, Giordano A, Desai D, Yamashita K, Harper JW, Elledge S, Nishimoto T, Morgan DO, Franza BR and Roberts JM: Formation and activation of a cyclin E-cdk2 complex during the G1 phase of the human cell cycle. Science. 257:1689–1694. 1992. View Article : Google Scholar : PubMed/NCBI
4	Dulić V, Lee E and Reed SI: Association of human cyclin E with a periodic G1-S phase protein kinase. Science. 257:1958–1961. 1992. View Article : Google Scholar : PubMed/NCBI
5	Lew DJ, Dulić V and Reed SI: Isolation of three novel human cyclins by rescue of G1 cyclin (Cln) function in yeast. Cell. 66:1197–1206. 1991. View Article : Google Scholar : PubMed/NCBI
6	Coulonval K, Bockstaele L, Paternot S and Roger PP: Phosphorylations of cyclin-dependent kinase 2 revisited using two-dimensional gel electrophoresis. J Biol Chem. 278:52052–52060. 2003. View Article : Google Scholar : PubMed/NCBI
7	Wan F, Weaver A, Gao X, Bern M, Hardwidge PR and Lenardo MJ: IKKβ phosphorylation regulates RPS3 nuclear translocation and NF-κB function during infection with Escherichia coli strain O157:H7. Nat Immunol. 12:335–343. 2011. View Article : Google Scholar : PubMed/NCBI
8	Morgan DO: Cyclin-dependent kinases: Engines, clocks, and microprocessors. Annu Rev Cell Dev Biol. 13:261–291. 1997. View Article : Google Scholar : PubMed/NCBI
9	Adams PD, Sellers WR, Sharma SK, Wu AD, Nalin CM and Kaelin WG Jr: Identification of a cyclin-cdk2 recognition motif present in substrates and p21-like cyclin-dependent kinase inhibitors. Mol Cell Biol. 16:6623–6633. 1996. View Article : Google Scholar : PubMed/NCBI
10	Martin A, Odajima J, Hunt SL, Dubus P, Ortega S, Malumbres M and Barbacid M: Cdk2 is dispensable for cell cycle inhibition and tumor suppression mediated by p27(Kip1) and p21(Cip1). Cancer Cell. 7:591–598. 2005. View Article : Google Scholar : PubMed/NCBI
11	Kim SH, Lee JY and Kim J: Characterization of a wide range base-damage-endonuclease activity of mammalian rpS3. Biochem Biophys Res Commun. 328:962–967. 2005. View Article : Google Scholar : PubMed/NCBI
12	Hegde V, Kelley MR, Xu Y, Mian IS and Deutsch WA: Conversion of the bifunctional 8-oxoguanine/beta-delta apurinic/apyrimidinic DNA repair activities of Drosophila ribosomal protein S3 into the human S3 monofunctional beta-elimination catalyst through a single amino acid change. J Biol Chem. 276:27591–27596. 2001. View Article : Google Scholar : PubMed/NCBI
13	Gao X and Hardwidge PR: Ribosomal protein S3: A multifunctional target of attaching/effacing bacterial pathogens. Front Microbiol. 2:1372011. View Article : Google Scholar : PubMed/NCBI
14	Warner J and McIntosh KB: How common are extraribosomal functions of ribosomal protein? Mol Cell. 34:3–11. 2009. View Article : Google Scholar : PubMed/NCBI
15	Zimmermann RA: The double life of ribosomal proteins. Cell. 15:130–132. 2003. View Article : Google Scholar
16	Naora H: Involvement of ribosomal proteins in regulating cell growth and apoptosis: Translational modulation or recruitment for extraribosomal activity? Immunol Cell Biol. 77:197–205. 1999. View Article : Google Scholar : PubMed/NCBI
17	Kim J, Chubatsu LS, Admon A, Stahl J, Fellous R and Linn S: Implication of mammalian ribosomal protein S3 in the processing of DNA damage. J Biol Chem. 270:13620–13629. 1995. View Article : Google Scholar : PubMed/NCBI
18	Kim TS, Kim HD and Kim J: PKCdelta-dependent functional switch of rpS3 between translation and DNA repair. J Biochim Biophys Acta. 1793:395–405, 1793. 2009. View Article : Google Scholar
19	Kim TS, Kim HD, Shin HS and Kim J: Phosphorylation status of nuclear ribosomal protein S3 is reciprocally regulated by protein kinase C{delta} and protein phosphatase 2A. J Biol Chem. 284:21201–21208. 2009. View Article : Google Scholar : PubMed/NCBI
20	Lee SB, Kwon IS, Park J, Lee KH, Ahn Y, Lee C, Kim J, Choi SY, Cho SW and Ahn JY: Ribosomal protein S3, a new substrate of Akt, serves as a signal mediator between neuronal apoptosis and DNA repair. J Bio Chem. 285:29457–29468. 2010. View Article : Google Scholar
21	Yoon IS, Chung JH, Hahm SH, Park MJ, Lee YR, Ko SI, Kang LW, Kim TS, Kim J and Han YS: Ribosomal protein S3 is phosphorylated by Cdk1/cdc2 during G2/M phase. BMB Rep. 8:529–534. 2011. View Article : Google Scholar
22	Spandari S, Sala F and Pedrali-Noy G: Aphidicolin: A specific inhibitor of nuclear DNA replication in eukaryotes. Trends Biochem Sci. 7:29–32. 1982. View Article : Google Scholar
23	Harper JV: Synchronization of cell population in G1/S and G2/M phases of the cell cycle. Methods Mol Biol. 296:157–166. 2005.PubMed/NCBI
24	Cude K, Wang Y, Choi HJ, Hsuan SL, Zhang H, Wang CY and Xia Z: Regulation of the G2-M cell cycle progression by the ERK5-NFkappaB signaling pathway. J Cell Biol. 177:253–264. 2007. View Article : Google Scholar : PubMed/NCBI
25	Watanabe N, Broome M and Hunter T: Regulation of the human WEE1Hu CDK tyrosine 15-kinase during the cell cycle. EMBO J. 14:1878–1891. 1995.PubMed/NCBI
26	Malumbers M and Barbacid M: To cycle or not to cycle: A critical decision in cancer. Nat Rev Cancer. 1:222–231. 2001. View Article : Google Scholar : PubMed/NCBI
27	Malumbers M and Barbacid M: Mammalian cyclin-dependent kinases. Trends Biochem Sci. 30:630–641. 2005. View Article : Google Scholar : PubMed/NCBI
28	Ecans T, Rosethal ET, Youngblom J, Distel D and Hunt T: Cyclin: A protein specificed by maternal mRNA in sea urchin eggs that is destroyed at each cleavage division. Cell. 33:389–396. 1983. View Article : Google Scholar : PubMed/NCBI
29	Salaun P, Rannou Y and Prigent C: Cdk1, Plks, Auroras and Neks: The mitotic bodyguards. Adv Exp Med Biol. 617:41–56. 2008. View Article : Google Scholar : PubMed/NCBI
30	Yacoub A, Augen L, Kelley MR, Doetsch PW and Deutsch WA: A Drosophila ribosomal protein contains 8-oxoguanine and abasic site DNA repair activities. EMBO J. 15:2306–2312. 1996.PubMed/NCBI
31	Deutsch WA, Yacoub A, Jaruga P, Zastawny TH and Disdaroglu M: Characterization and mechanism of action of Drosophila ribosomal protein S3 DNA glycosylase activity for the removal of oxidatively damage DNA bases. J Biol Chem. 272:32857–32860. 1997. View Article : Google Scholar : PubMed/NCBI
32	Ko SI, Park JH, Park MJ, Kim J, Kang LW and Han YS: Human ribosomal protein S3 (hRpS3) interacts with uracil-DNA glycosylase (hUNG) and stimulates its glycosylase activity. Mutat Res. 648:54–64. 2008. View Article : Google Scholar : PubMed/NCBI
33	Hegde V, Wang M and Deutsch WA: Human ribosomal protein S3 interacts with DNA base excision repair protein hAPE/Ref-1 and hOGG1. Biochemistry. 43:14211–14217. 2004. View Article : Google Scholar : PubMed/NCBI
34	Bernstein KA and Baserga SJ: The small subunit processome is required for cell cycle progression at G1. Mol Biol Cell. 15:5038–5046. 2004. View Article : Google Scholar : PubMed/NCBI
35	Guo X, Shi Y, Gou Y, Li J, Han S, Zhang Y, Huo J, Ning X, Sun L, Chen Y, et al: Human ribosomal protein S13 promotes gastric cancer growth through down-regulating p27 (Kip1). J Cell Mol Med. 15:296–306. 2011. View Article : Google Scholar : PubMed/NCBI