This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Basu, U. Articles by Maitra, U. Search for Related Content PubMed PubMed Citation Articles by Basu, U. Articles by Maitra, U.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, September 2003, p. 6187-6199, Vol. 23, No. 17
0270-7306/03/$08.00+0     DOI: 10.1128/MCB.23.17.6187-6199.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Phosphorylation of Mammalian Eukaryotic Translation Initiation Factor 6 and Its Saccharomyces cerevisiae Homologue Tif6p: Evidence that Phosphorylation of Tif6p Regulates Its Nucleocytoplasmic Distribution and Is Required for Yeast Cell Growth

Uttiya Basu, Kausik Si, Haiteng Deng, and Umadas Maitra^*

Department of Developmental and Molecular Biology, Albert Einstein College of Medicine of Yeshiva University, Bronx, New York 10461

Received 16 May 2003/ Accepted 6 June 2003

The synthesis of 60S ribosomal subunits in Saccharomyces cerevisiae requires Tif6p, the yeast homologue of mammalian eukaryotic translation initiation factor 6 (eIF6). In the present work, we have isolated a protein kinase from rabbit reticulocyte lysates on the basis of its ability to phosphorylate recombinant human eIF6. Mass spectrometric analysis as well as antigenic properties of the purified kinase identified it as casein kinase I. The site of in vitro phosphorylation, which is highly conserved from yeast to mammals, was identified as the serine residues at positions 174 (major site) and 175 (minor site). The homologous yeast protein Tif6p was also phosphorylated in vivo in yeast cells. Mutation of Tif6p at serine-174 to alanine reduced phosphorylation drastically and caused loss of cell growth and viability. When both Ser-174 and Ser-175 were mutated to alanine, phosphorylation of Tif6p was completely abolished. Furthermore, while wild-type Tif6p was distributed both in nuclei and the cytoplasm of yeast cells, the mutant Tif6p (with Ser174Ala and Ser175Ala) became a constitutively nuclear protein. These results suggest that phosphorylatable Ser-174 and Ser-175 play a critical role in the nuclear export of Tif6p.

---

* Corresponding author. Mailing address: Department of Developmental and Molecular Biology, Albert Einstein College of Medicine of Yeshiva University, 1300 Morris Park Ave., Bronx, NY 10461. Phone: (718) 430-3505. Fax: (718) 430-8567. E-mail: maitra{at}aecom.yu.edu.

This paper is dedicated to the loving memory of Amar Bhadhuri. He was an outstanding scientist and an extraordinary human being who inspired many students and scientists in India, by advice and example, to do research for the advancement of knowledge.

Present address: Howard Hughes Medical Institute and Center for Neurobiology, Columbia University College of Physicians and Surgeons, New York, NY 10032.

---

Molecular and Cellular Biology, September 2003, p. 6187-6199, Vol. 23, No. 17
0022-538X/03/$08.00+0     DOI: 10.1128/MCB.23.17.6187-6199.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

This article has been cited by other articles:

• Benelli, D., Marzi, S., Mancone, C., Alonzi, T., la Teana, A., Londei, P. (2009). Function and ribosomal localization of aIF6, a translational regulator shared by archaea and eukarya. Nucleic Acids Res 37: 256-267 [Abstract] [Full Text]  
• Hong, C. I., Ruoff, P., Loros, J. J., Dunlap, J. C. (2008). Closing the circadian negative feedback loop: FRQ-dependent clearance of WC-1 from the nucleus. Genes Dev. 22: 3196-3204 [Abstract] [Full Text]  
• Ray, P., Basu, U., Ray, A., Majumdar, R., Deng, H., Maitra, U. (2008). The Saccharomyces cerevisiae 60 S Ribosome Biogenesis Factor Tif6p Is Regulated by Hrr25p-mediated Phosphorylation. J. Biol. Chem. 283: 9681-9691 [Abstract] [Full Text]