Cell Growth & Differentiation, Vol 3, Issue 7 413-420, Copyright © 1992 by American Association of Cancer Research

ARTICLES

Expression and phosphorylation of the retinoblastoma protein during induced differentiation of murine erythroleukemia cells

VM Richon, RA Rifkind and PA Marks
DeWitt Wallace Research Laboratory, Memorial Sloan-Kettering Cancer Center, Cornell University, New York, New York 10021.

Phosphorylation and dephosphorylation of the retinoblastoma protein, pRB, play a role in the control of cell cycle progression and expression of differentiation in eukaryotic cells. The regulation of pRB level and phosphorylation state was investigated during the induction of differentiation of murine erythroleukemia cells (MELC) by the chemical agent hexamethylene bisacetamide (HMBA). In MELC, there is a critical time in G1 or early S phase when HMBA must be present in order to induce differentiation. This is followed by prolongation of the subsequent G1 phase, resumption of progression through the cell cycle for several generations, and then cell cycle arrest in G1-G0. Associated with HMBA-induced prolongation of G1, there is an increase in the amount of the underphosphorylated form of pRB. A variant cell line (DS19/VCR-C) with accelerated kinetics of HMBA-mediated differentiation shows a more marked increase in underphosphorylated pRB. In culture with HMBA, as MELC resume progression through the cell cycle, pRB is present in the phosphorylated form. The total amount of pRB increases approximately 3-fold over the succeeding cell divisions prior to terminal arrest in G1. This increase in pRB is inhibited by dexamethasone, which also blocks HMBA-induced MELC differentiation. During this period, RB mRNA also increases approximately 3- to 5-fold, which reflects an increase in the rate of transcription, with no change in mRNA stability. The state of phosphorylation and amount of pRB appear to be involved in the control of HMBA-induced terminal cell division of MELC.

This article has been cited by other articles:

				M. Sekimata and Y. Homma Sequence-specific transcriptional repression by an MBD2-interacting zinc finger protein MIZF Nucleic Acids Res., January 29, 2004; 32(2): 590 - 597. [Abstract] [Full Text] [PDF]

				P. N. Munster, T. Troso-Sandoval, N. Rosen, R. Rifkind, P. A. Marks, and V. M. Richon The Histone Deacetylase Inhibitor Suberoylanilide Hydroxamic Acid Induces Differentiation of Human Breast Cancer Cells Cancer Res., December 1, 2001; 61(23): 8492 - 8497. [Abstract] [Full Text] [PDF]

				N. O. Fortunel, A. Hatzfeld, and J. A. Hatzfeld Transforming growth factor-beta : pleiotropic role in the regulation of hematopoiesis Blood, September 15, 2000; 96(6): 2022 - 2036. [Abstract] [Full Text] [PDF]

				A. Kimura, M. Ohmichi, H. Kurachi, H. Ikegami, J. Hayakawa, K. Tasaka, Y. Kanda, Y. Nishio, H. Jikihara, N. Matsuura, et al. Role of Mitogen-activated Protein Kinase/Extracellular Signal-regulated Kinase Cascade in Gonadotropin-releasing Hormone-induced Growth Inhibition of a Human Ovarian Cancer Cell Line Cancer Res., October 1, 1999; 59(20): 5133 - 5142. [Abstract] [Full Text] [PDF]

				M. Alcalay, L. Tomassoni, E. Colombo, S. Stoldt, F. Grignani, M. Fagioli, L. Szekely, K. Helin, and P. G. Pelicci The Promyelocytic Leukemia Gene Product (PML) Forms Stable Complexes with the Retinoblastoma Protein Mol. Cell. Biol., February 1, 1998; 18(2): 1084 - 1093. [Abstract] [Full Text]

				S. Desrivieres, S. Desrivières, and S. Ferrari Evidence for Different Mechanisms of Growth Inhibition of T-cell Lymphoma by Phorbol Esters and Concanavalin A J. Biol. Chem., January 24, 1997; 272(4): 2470 - 2476. [Abstract] [Full Text] [PDF]

				S Salzberg, A Heller, J. Zou, F. Collart, and E Huberman Interferon-independent activation of (2'-5') oligoadenylate synthetase in Friend erythroleukemia cell variants exposed to HMBA J. Cell Sci., January 6, 1996; 109(6): 1517 - 1526. [Abstract] [PDF]

				K F Macleod, N Sherry, G Hannon, D Beach, T Tokino, K Kinzler, B Vogelstein, and T Jacks p53-dependent and independent expression of p21 during cell growth, differentiation, and DNA damage. Genes & Dev., April 15, 1995; 9(8): 935 - 944. [Abstract] [PDF]