Abstract
Cytokine response gene 6 (CR6), cloned from interleukin 2-stimulated T lymphocytes, is homologous to GADD45 and MyD118, genes which promote cell cycle arrest and apoptosis. To determine how this gene family could possibly mediate both cell survival/proliferation and cell cycle arrest/death, transfectants were generated so that the genes could be expressed ectopically, independently from their normal inducing agents. In cycling retinoblastoma protein-negative (pRb-) cells, ectopic CR6 expression blocked G2/M transition, but did not prevent G1/S transition so that endoreduplication resulted. By comparison, when CR6, GADD45, and MyD118 genes were expressed ectopically in proliferating pRb+ cells, either G1/S or G2/M transition was effectively blocked, so that there was no endoreduplication. Consistent with these findings, in proliferating pRb-cells, ectopic expression of CR6 promoted the expression of both G1 and G2/M cyclins. By comparison, in pRb+ cells, the expression of G1 cyclins was increased, while expression of the mitotic cyclins was decreased. However, in pRb+ cells, cyclin-dependent kinase activities associated with both G1 and G2/M cyclins were decreased. Moreover, ectopic expression of all three genes resulted in the expression of the CKI, p21, both in pRb- and pRb+ cells. The physiologic induction of CR6 expression by IL2 in quiescent normal human T cells occurs transiently in the first half of G1, coordinately with the expression of p21. Therefore, this gene family regulates G1 and G2, and promotes either cell growth or arrest by a common mechanism.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 6573-6582 |
| Number of pages | 10 |
| Journal | Oncogene |
| Volume | 18 |
| Issue number | 47 |
| State | Published - Nov 11 1999 |
| Externally published | Yes |
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Keywords
- Cell cycle
- Cytokine
- G1 and G2 progression
ASJC Scopus subject areas
- Molecular Biology
- Cancer Research
- Genetics
Cite this
Cytokine response gene 6 induces p21 and regulates both cell growth and arrest. / Fan, Wen; Richter, Gunther; Cereseto, Anna; Beadling, Carol; Smith, Kendall A.
In: Oncogene, Vol. 18, No. 47, 11.11.1999, p. 6573-6582.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Cytokine response gene 6 induces p21 and regulates both cell growth and arrest
AU - Fan, Wen
AU - Richter, Gunther
AU - Cereseto, Anna
AU - Beadling, Carol
AU - Smith, Kendall A.
PY - 1999/11/11
Y1 - 1999/11/11
N2 - Cytokine response gene 6 (CR6), cloned from interleukin 2-stimulated T lymphocytes, is homologous to GADD45 and MyD118, genes which promote cell cycle arrest and apoptosis. To determine how this gene family could possibly mediate both cell survival/proliferation and cell cycle arrest/death, transfectants were generated so that the genes could be expressed ectopically, independently from their normal inducing agents. In cycling retinoblastoma protein-negative (pRb-) cells, ectopic CR6 expression blocked G2/M transition, but did not prevent G1/S transition so that endoreduplication resulted. By comparison, when CR6, GADD45, and MyD118 genes were expressed ectopically in proliferating pRb+ cells, either G1/S or G2/M transition was effectively blocked, so that there was no endoreduplication. Consistent with these findings, in proliferating pRb-cells, ectopic expression of CR6 promoted the expression of both G1 and G2/M cyclins. By comparison, in pRb+ cells, the expression of G1 cyclins was increased, while expression of the mitotic cyclins was decreased. However, in pRb+ cells, cyclin-dependent kinase activities associated with both G1 and G2/M cyclins were decreased. Moreover, ectopic expression of all three genes resulted in the expression of the CKI, p21, both in pRb- and pRb+ cells. The physiologic induction of CR6 expression by IL2 in quiescent normal human T cells occurs transiently in the first half of G1, coordinately with the expression of p21. Therefore, this gene family regulates G1 and G2, and promotes either cell growth or arrest by a common mechanism.
AB - Cytokine response gene 6 (CR6), cloned from interleukin 2-stimulated T lymphocytes, is homologous to GADD45 and MyD118, genes which promote cell cycle arrest and apoptosis. To determine how this gene family could possibly mediate both cell survival/proliferation and cell cycle arrest/death, transfectants were generated so that the genes could be expressed ectopically, independently from their normal inducing agents. In cycling retinoblastoma protein-negative (pRb-) cells, ectopic CR6 expression blocked G2/M transition, but did not prevent G1/S transition so that endoreduplication resulted. By comparison, when CR6, GADD45, and MyD118 genes were expressed ectopically in proliferating pRb+ cells, either G1/S or G2/M transition was effectively blocked, so that there was no endoreduplication. Consistent with these findings, in proliferating pRb-cells, ectopic expression of CR6 promoted the expression of both G1 and G2/M cyclins. By comparison, in pRb+ cells, the expression of G1 cyclins was increased, while expression of the mitotic cyclins was decreased. However, in pRb+ cells, cyclin-dependent kinase activities associated with both G1 and G2/M cyclins were decreased. Moreover, ectopic expression of all three genes resulted in the expression of the CKI, p21, both in pRb- and pRb+ cells. The physiologic induction of CR6 expression by IL2 in quiescent normal human T cells occurs transiently in the first half of G1, coordinately with the expression of p21. Therefore, this gene family regulates G1 and G2, and promotes either cell growth or arrest by a common mechanism.
KW - Cell cycle
KW - Cytokine
KW - G1 and G2 progression
UR - http://www.scopus.com/inward/record.url?scp=0033547359&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0033547359&partnerID=8YFLogxK
M3 - Article
VL - 18
SP - 6573
EP - 6582
JO - Oncogene
JF - Oncogene
SN - 0950-9232
IS - 47
ER -