INHIBITION OF THE G1-S TRANSITION OF THE CELL-CYCLE BY INHIBITORS OF DEOXYHYPUSINE HYDROXYLATION

被引:130
作者
HANAUSKEABEL, HM
PARK, MH
HANAUSKE, AR
POPOWICZ, AM
LALANDE, M
FOLK, JE
机构
[1] NIDR,CELLULAR DEV & ONCOL LAB,BETHESDA,MD 20892
[2] TECH UNIV MUNICH,DEPT MED 1,DIV HEMATOL ONCOL,W-8000 MUNICH 80,GERMANY
[3] ROCKEFELLER UNIV,COMP SERV,NEW YORK,NY 10021
[4] HARVARD UNIV,CHILDRENS HOSP,SCH MED,HOWARD HUGHES MED INST,BOSTON,MA 02115
[5] HARVARD UNIV,CHILDRENS HOSP,SCH MED,DIV GENET,BOSTON,MA 02115
来源
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH | 1994年 / 1221卷 / 02期
关键词
MIMOSINE; CELL CYCLE; POSTTRANSLATIONAL MODIFICATION; HYPUSINE;
D O I
10.1016/0167-4889(94)90003-5
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The formation of the unusual amino-acid hypusine in eIF-5A (eukaryotic initiation factor 5A) is associated with cellular proliferation. We used a panel of compounds, including mimosine, to probe the relationship between the exit from the GI phase of the cell cycle, i.e., the onset of DNA replication, and the formation of hypusine by the enzyme deoxyhypusyl hydroxylase (DOHH). These two parameters displayed the same dose dependency and structure-activity relationship. Only compounds that inhibited DOHH also suppressed proliferation. This effect was observed: (i) in spontaneously proliferating, virally transformed, and mitogen-stimulated cells; (ii) for both anchorage-dependent and anchorage-independent proliferation; and (iii) with normal and malignant cell lines. DOHH reactivation occurred rapidly after inhibitor withdrawal and correlated with synchronized entry into S. The changes in the expression of specific genes during the G1-to-S transition mimicked the physiological pattern. These findings suggest that hypusine formation in eIF-5A which occurs in a specific, invariant sequence motif acquired early in evolution, may be involved in the G1-to-S transition in the eukaryotic cells tested.
引用
收藏
页码:115 / 124
页数:10
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