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Blood, 1 November 2005, Vol. 106, No. 9, pp. 3256-3263. Prepublished online as a Blood First Edition Paper on June 28, 2005; DOI 10.1182/blood-2003-10-3458. This Article Full Text (PDF) All Versions of this Article: 2003-10-3458v1 106/9/3256    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Tang, D. C Articles by Rodgers, G. P Search for Related Content PubMed PubMed Citation Articles by Tang, D. C Articles by Rodgers, G. P Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted October 14, 2003 Accepted June 21, 2005 The hydroxyurea-induced small GTP-binding protein SAR modulates -globin gene expression in human erythroid cells Delia C Tang, Jianqiong Zhu, Wenli Liu, Kyung Chin, Jun Sun, Ling Chen, John A Hanover, and Griffin P Rodgers* Molecular and Clinical Hematology Branch, National Institutes of Health, BETHESDA, MD, USA Laboratory of Cell Biochemistry, National Institutes of Health, BETHESDA, MD, USA * Corresponding author; email: gr5n{at}nih.gov. Hydroxyurea (HU), a drug effective in the treatment of sickle cell disease, is thought to indirectly promote fetal hemoglobin (Hb F) production by perturbing the maturation of erythroid precursors. The molecular mechanisms involved in HU-mediated regulation of -globin expression are currently unclear. We identified an HU-induced small GTP-binding protein, secretion-associated and ras-related (SAR), in adult erythroid cells using differential display. Stable SAR expression in K562 cells increased -globin mRNA expression and resulted in macrocytosis and cells that appeared immature. SAR-mediated induction of -globin also inhibited K562 cell growth by causing arrest in G1/S, apoptosis, and delay of maturation, cellular changes consistent with the previously known effects of HU on erythroid cells. SAR also enhanced both - and -globin transcription in primary bone marrow CD34+ cells, with a greater effect on -globin than on -globin. Though upregulation of GATA-2 and p21 were observed both in SAR-expressing cells and HU-treated K562 cells, PI3 kinase and phosphorylated ERK were inhibited specifically in SAR-expressing cells. These data reveal a novel role of SAR distinct from its previously known protein trafficking function. We suggest that SAR may participate in both erythroid cell growth and -globin production by regulating PI3 kinase/ERK and GATA-2/p21-dependent signal transduction pathways. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. L. Thein, S. Menzel, X. Peng, S. Best, J. Jiang, J. Close, N. Silver, A. Gerovasilli, C. Ping, M. Yamaguchi, et al. Intergenic variants of HBS1L-MYB are responsible for a major quantitative trait locus on chromosome 6q23 influencing fetal hemoglobin levels in adults PNAS, July 3, 2007; 104(27): 11346 - 11351. [Abstract] [Full Text] [PDF] A. Bank Regulation of human fetal hemoglobin: new players, new complexities Blood, January 15, 2006; 107(2): 435 - 443. [Abstract] [Full Text] [PDF]

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