The Major Protein of Messenger Ribonucleoprotein Particles in Somatic Cells Is a Member of the Y-box Binding Transcription Factor Family

Evdokimova, Valentina; Wei, Chia‐Lin; Sitikov, Albert; Simonenko, Peter N.; Lazarev, Oleg A.; Vasilenko, Konstantin S.; Ustinov, Valentin; Hershey, John W.B.; Ovchinnikov, Lev P.

doi:10.1074/jbc.270.7.3186

Cited by 162 publications

(157 citation statements)

References 30 publications

Supporting

Mentioning

147

Contrasting

Order By: Relevance

“…21 We have shown that YB-1 recognizes the inverted CCAAT box as well as cisplatin-modified DNA. 5 YB-1 is a major core protein of messenger ribonucleoprotein particles, 22 and its overexpression in mammalian cells inhibits protein synthesis. 23 It has been shown to bind specifically to RNA containing 8-oxoguanine, 24 suggesting that it may function to sequester oxidatively damaged mRNA molecules from the translational machinery.…”

Section: Figurementioning

confidence: 99%

ZNF143 activates gene expression in response to DNA damage and binds to cisplatin‐modified DNA

Ishiguchi

Izumi

Torigoe

et al. 2004

Intl Journal of Cancer

View full text Add to dashboard Cite

We have identified a cisplatin-inducible gene, the mitochondrial ribosomal protein S11 (MRP S11) gene, by means of mRNA differential display. Functional analysis of the MRP S11 promoter showed that a Staf binding site in the promoter is required for both basal promoter activity and cisplatin-inducible activity. We also found that Cisplatin is a widely used anticancer agent, and DNA damage is believed to be the main basis of the antitumor effect of cisplatin. Since cisplatin resistance is a major obstacle to the treatment of solid tumors, understanding the molecular basis of the DNA damage response and of cisplatin resistance is important for clinical protocols. Cisplatin resistance is thought to involve several mechanisms, including increased drug efflux, the presence of cellular thiols, increased nucleotide excision repair activity and decreased mismatch repair activity. [1][2][3][4] In addition, several mechanisms are thought to contribute to the DNA damage response associated with cisplatin resistance. To understand fully these molecular mechanisms, it is desirable to identify and characterize all the transcription factors that are activated by DNA damage. We have previously shown that transcription factors such as Y-box binding protein (YB-1) and the CCAAT-binding transcription factor 2 (CTF2) are overexpressed in human cancer cell lines resistant to cisplatin. 5,6 YB-1 has been shown to bind preferentially to cisplatin-modified DNA 5 and is activated by nuclear translocation and by transcriptional mechanisms. Oct1 participates in the cellular response to DNA damage, 7,8 and its induction involves posttranscriptional mechanisms. Both c-Myc and AP-1 are also activated and involved in cellular responses to cisplatin. 8 One cisplatininducible cDNA clone has been shown to encode the vacuolar H ϩ -ATPase subunit c (ATP6L), 9,10 and analysis of its expression revealed that both Sp1 and Oct1 are critical for its activation by anticancer agents. 11 In order to identify novel mechanisms involved in the DNA damage response, we have used differential display to compare gene expression between control and cisplatin-treated cells. Here, we characterize one cisplatin-inducible gene, MRP S11, whose product, MRP S11, is a component of the ribosomal small subunit and binds to 12S rRNA. 12 MRP S11 appears to have RNA binding but not DNA binding activity. We have isolated the promoter region of MRP S11 in order to identify its transcriptional activators. Functional analysis revealed a critical Staf binding site in the core of the promoter. The zinc finger transcription factor, Staf, originally identified in the frog, is involved in transcriptional regulation of snRNA type and mRNA promoters transcribed either by RNA polymerase II or III. 13 Two human homologues of Staf, ZNF 76 and ZNF 143, have been isolated. 14 Here we show that activation of the transcriptional activator ZNF 143 upregulates the transcription of MRP S11. We present evidence that ZNF 143, but not ZNF 76, is induced by DNA damage. We further demonstrate that ZN...

show abstract

Section: Figurementioning

confidence: 99%

ZNF143 activates gene expression in response to DNA damage and binds to cisplatin‐modified DNA

Ishiguchi

Izumi

Torigoe

et al. 2004

Intl Journal of Cancer

View full text Add to dashboard Cite

show abstract

“…It is also present in mRNPs derived from polysomes, but in lower amounts (9,10). Regardless of the fact that p50 displayed little or no specificity for RNA in in vitro binding experiments (10,11), in cell extracts, p50 was found only in association with mRNA (12). This protein is located mostly in the cytoplasm, and its amount is ϳ0.1% of the total protein, which corresponds to ϳ5-10 molecules of p50/molecule of mRNA (12).…”

mentioning

confidence: 97%

“…Among all mRNP proteins, p50 is the most basic, with a pI of ϳ9.5 (10). In the absence of RNA, p50 forms large multimeric complexes with a molecular mass of ϳ800 kDa (11). When binding to mRNA, p50 melts up to 60% of the RNA secondary structure (11).…”

mentioning

confidence: 99%

“…In the absence of RNA, p50 forms large multimeric complexes with a molecular mass of ϳ800 kDa (11). When binding to mRNA, p50 melts up to 60% of the RNA secondary structure (11). We have shown earlier that p50 is responsible for the repressed nonactive state of globin mRNA within free mRNPs (13) and that it strongly inhibits translation of exogenous mRNA in cell-free translation systems (9,14) as well as in vivo translation of mRNA expressed from a reporter gene (12).…”

mentioning

confidence: 99%

“…According to its amino acid sequence and its affinity for DNA, p50 was identified as a member of the most evolutionarily conserved family of Y-box-binding proteins from bacteria to man (11). Some proteins of this family are known as transcription factors affecting transcription of genes containing Y-box sequence elements in their promoters (15)(16)(17).…”

mentioning

confidence: 99%

See 2 more Smart Citations

The Major Core Protein of Messenger Ribonucleoprotein Particles (p50) Promotes Initiation of Protein Biosynthesis in Vitro

Evdokimova¹,

Kovrigina²,

Nashchekin³

et al. 1998

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

The major core protein of cytoplasmic messenger ribonucleoprotein particles (p50) has been shown previously to inhibit protein synthesis in vitro and in vivo. Furthermore, p50 is highly homologous to the Y-boxbinding transcription factor family of proteins, binds DNA containing the Y-box motif, and thus may have a dual function in cells as a regulator of both transcription and translation. Here we show that binding or removal of p50 from rabbit reticulocyte lysate by monospecific antibodies to p50 strongly inhibits translation of endogenous and exogenous globin mRNAs as well as prokaryotic ␤-galactosidase mRNA in a rabbit reticulocyte cell-free system. Thus, depending on the conditions, p50 not only may act as a translational repressor, but may also be required for protein synthesis. Translation inhibition with anti-p50 antibodies is not a result of mRNA degradation or its functional inactivation. The inhibition does not change the ribosome transit time, and therefore, it does not affect elongation/termination of polypeptide chains. The inhibition with anti-p50 antibodies is followed by a decay of polysomes and accumulation of the 48 S preinitiation complex. These results suggest that p50 participates in initiation of protein biosynthesis. Although uninvolved in the formation of the 48 S preinitiation complex, p50 is necessary either for attachment of the 60 S ribosomal subunit or for previous 5 -untranslated region scanning by the 43 S preinitiation complex.

show abstract

Patterns of translational regulation in the mammalian testis

Kleene¹

1996

Mol. Reprod. Dev.

170

View full text Add to dashboard Cite

The translational activity of more than 40 different mRNAs in rodent testes has been analyzed by determining the proportions of inactive free‐mRNPs and active polysomal mRNAs in sucrose gradients. These mRNAs can be sorted into several groups comprising mRNAs with similar patterns of translational activity in particular cell types. mRNAs in testicular somatic cells sediment primarily with polysomes, indicating that they are translated efficiently, whereas the vast majority of mRNAs in late meiotic and haploid spermatogenic cells display high levels of free‐mRNPs, indicative of a block to the initiation of translation. Protamine mRNAs exemplify a group of mRNAs that is transcribed in round spermatids, stored as free‐mRNPs for several days, and translated in elongated spermatids after the cessation of transcription. The extent to which the free‐mRNPs in primary spermatocytes and round spermatids are due to developmental changes in translational activity is unclear. mRNAs at these stages can often be detected earlier than the corresponding protein, implicating either a delay in translational activation or difficulties in detecting the protein. In contrast, sucrose gradients consistently indicate little difference in the proportions of various mRNAs in free‐mRNPs in primary spermatocytes and round spermatids, implying that the proportions of translationally active mRNAs remain essentially constant. Since the levels of some mRNAs appear to greatly exceed the amount that is translated, the biological significance of some free‐mRNPs in meiotic and early haploid cells in unclear. There are numerous examples of controls over the translation of individual mRNAs in meiotic and haploid cells; the proportions of various mRNAs in free‐mRNPs range from virtually none to virtually all, and individual mRNAs are activated at specific stages in elongated spermatids. Existing evidence is contradictory whether the mRNAs in the protamine/transition protein gene family are repressed by mRNP proteins of sequestration. © 1996 Wiley‐Liss, Inc.

show abstract

The Major Protein of Messenger Ribonucleoprotein Particles in Somatic Cells Is a Member of the Y-box Binding Transcription Factor Family

Cited by 162 publications

References 30 publications

ZNF143 activates gene expression in response to DNA damage and binds to cisplatin‐modified DNA

ZNF143 activates gene expression in response to DNA damage and binds to cisplatin‐modified DNA

The Major Core Protein of Messenger Ribonucleoprotein Particles (p50) Promotes Initiation of Protein Biosynthesis in Vitro

Patterns of translational regulation in the mammalian testis

Contact Info

Product

Resources

About