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Alternative reading frames of the INK4a tumor suppressor gene encode two unrelated proteins capable of inducing cell cycle arrest

Article Abstract:

The INK4a gene encodes an inhibitor (p16(superINK4a)) of the cyclin D-dependent kinases CDK4 and CDK6 that prevents them from phosphorylating the retinoblastoma protein and obstructs exit from the G1 phase of the cell cycle. The inhibitor negatively affects the growth of the tumors. An unrelated protein (p19(superARF)) arises in major part from an alternative reading frame of the mouse gene. Unitary inheritance of these two proteins signifies their dual requirement in the cell cycle control.

Author: Sherr, Charles J., Zindy, Frederique, Quelle, Dawn E., Ashmun, Richard A.
Publisher: Elsevier B.V.
Publication Name: Cell
Subject: Biological sciences
ISSN: 0092-8674
Year: 1995
Analysis, Physiological aspects, Proteins, Gene expression, Cell cycle

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AML1, the target of multiple chromosomal translocation in human leukemia, is essential for normal fetal liver hematopoiesis

Article Abstract:

The function of the acute myeloid leukemia 1 (AML1)-core-binding factor beta heterodimeric trancription factor was studied using mice embryos that were homozygous for the mutation. Homozygous AML1 mutant embryos showed normal erythropoiesis but had defective fetal liver hematopoiesis. Further test which involved disrupting the AML1 allele in embryonic stem cells showed that the stems cells did not undergo hematopoiesis. The AML1 gene was shown to direct hematopoiesis.

Author: Downing, James R., Hiebert, Scott W., Okuda, Tsukasa,, van Deursen, Jan, Grosveld, Gerard
Publisher: Elsevier B.V.
Publication Name: Cell
Subject: Biological sciences
ISSN: 0092-8674
Year: 1996
Genetic aspects, Genetic regulation, Physiological regulation, Genetic transcription, Transcription (Genetics), Translocation (Genetics), Leukemia, Hematopoiesis

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Tumor suppression at the mouse INK4a locus mediated by the alternative reading frame product p19ARF

Article Abstract:

A frequently inactivated tumor suppressor gene in human cancer is INK4a, which encodes p16INK4a, which is a specific inhibitor of CDK4 and CDK6, cyclin D-dependent kinases. The ARF function in mice was selectively disrupted through the deletion of exon 1Beta and leaving all p16INK4a coding sequences. The results indicate that ARF and p53 regulate senescence of mouse embryo fibroblasts.

Author: Roussel, Martine F., Sherr, Charles J., Zindy, Frederique, Downing, James R., Quelle, Dawn E., Ashmun, Richard A., Grosveld, Gerard, Kamijo, Takehiko
Publisher: Elsevier B.V.
Publication Name: Cell
Subject: Biological sciences
ISSN: 0092-8674
Year: 1997
Tumor suppressor genes

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