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Prepublished online as a Blood First Edition Paper on March 13, 2003; DOI 10.1182/blood-2002-10-3149. This Article Full Text (PDF) All Versions of this Article: 2002-10-3149v1 102/1/254    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 Dimberg, A. I Articles by Oberg, F. G Search for Related Content PubMed PubMed Citation Articles by Dimberg, A. I Articles by Oberg, F. G Social Bookmarking                   What's this? Submitted October 17, 2002 Accepted February 11, 2003 Ser-727/Tyr-701 phosphorylated Stat1 is required for the regulation of c-Myc, cyclins, and p27Kip1 associated with ATRA-induced G0/G1 arrest of U-937 cells Anna I Dimberg, Inger Karlberg, Kenneth Nilsson, and Fredrik G Oberg* Department of Genetics and Pathology, Uppsala University, Uppsala, Sweden * Corresponding author; email: Fredrik.Oberg{at}genpat.uu.se. All-trans retinoic acid (ATRA)-induced growth arrest of myeloid cells is associated with a sequential regulation of cyclins and CKIs, which modulates the cell-cycle machinery and inhibits the G1-S phase progression. ATRA-treatment of myeloid cells induces up-regulation and tyrosine phosphorylation of Stat1, a member of the STAT transcription factor family that has been implicated in growth arrest in response to interferons. We have previously shown that ATRA-induced cell cycle arrest is dependent on tyrosine phosphorylated Stat1. In this study, we show that there is a basal level of Stat1 Ser-727 phosphorylation in U-937 cells, which is transiently increased in response to ATRA treatment. Using Stat1S727A expressing sublines, we provide evidence that Ser-727 phosphorylation of Stat1 is required for ATRA-induced growth arrest. To shed further light on the role of Stat1 in ATRA-induced cell cycle arrest, cyclin and CKI expression was analyzed during ATRA-treatment in U-937 sublines expressing Stat1S727A and Stat1Y701F. Our results show that Ser-727/Tyr-701 phosphorylated Stat1 plays a key role as a prerequisite for the ATRA-induced down-regulation of c-Myc, cyclins A, B, D2, D3 and E, and the simultaneous up-regulation of p27 Kip1, associated with arrest in the G0/G1 phase of the cell cycle. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. P. Treon, Z. R. Hunter, A. Aggarwal, E. P. Ewen, S. Masota, C. Lee, D. D. Santos, E. Hatjiharissi, L. Xu, X. Leleu, et al. Characterization of familial Waldenstrom's macroglobulinemia Ann. Onc., March 1, 2006; 17(3): 488 - 494. [Abstract] [Full Text] [PDF] C. Kardinal, M. Dangers, A. Kardinal, A. Koch, D. T. Brandt, T. Tamura, and K. Welte Tyrosine phosphorylation modulates binding preference to cyclin-dependent kinases and subcellular localization of p27Kip1 in the acute promyelocytic leukemia cell line NB4 Blood, February 1, 2006; 107(3): 1133 - 1140. [Abstract] [Full Text] [PDF] L. Lal, Y. Li, J. Smith, A. Sassano, S. Uddin, S. Parmar, M. S. Tallman, S. Minucci, N. Hay, and L. C. Platanias Activation of the p70 S6 kinase by all-trans-retinoic acid in acute promyelocytic leukemia cells Blood, February 15, 2005; 105(4): 1669 - 1677. [Abstract] [Full Text] [PDF] Y. Wang, M. G. Malabarba, Z. S. Nagy, and R. A. Kirken Interleukin 4 Regulates Phosphorylation of Serine 756 in the Transactivation Domain of Stat6: ROLES FOR MULTIPLE PHOSPHORYLATION SITES AND Stat6 FUNCTION J. Biol. Chem., June 11, 2004; 279(24): 25196 - 25203. [Abstract] [Full Text] [PDF]

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