|
|
Prepublished online as a Blood First Edition Paper on March 13, 2003; DOI 10.1182/blood-2002-10-3149.
 Previous Article | Table of Contents | Next Article 
Blood, 1 July 2003, Vol. 102, No. 1, pp. 254-261
NEOPLASIA
Ser727/Tyr701-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 Dimberg,
Inger Karlberg,
Kenneth Nilsson, and
Fredrik Öberg
From the Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Sweden.
All-trans retinoic acid (ATRA)—induced growth arrest of myeloid cells is associated with a sequential regulation of cyclins and cyclin-dependent kinase inhibitors (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 (signal transducer and activator of transcription) 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 tyrosinephosphorylated Stat1. In this study, we show that there is a basal level of Stat1 Ser727 phosphorylation in U-937 cells, which is transiently increased in response to ATRA treatment. Using Stat1Ser727Ala-expressing sublines, we provide evidence that Ser727 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 Stat1Ser727Ala and Stat1Tyr701Phe. Our results show that Ser727/Tyr701-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 p27Kip1, associated with arrest in the G0/G1 phase of the cell cycle. (Blood. 2003;102:254-261)
 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]
|
|
|
| |
