RT Journal Article
ID 3b024ef834e0fe49
A1 Meyers , Shari
A1 Hiebert, Scott W. 
T1 Indirect and Direct Disruption of Transcriptional Regulation in Cancer: E2F and AML-1
JF Critical Reviews™ in Eukaryotic Gene Expression
JO CRE
YR 1995
FD 1995-12-20
VO 5
IS 3-4
SP 365
OP 383
K1 AML-l
K1 E2F
K1 DP-1
K1 t(8;21)
K1 t(12;21),translocation
AB The disruption of transcriptional regulatory circuits through the elimination of negative regulatory factors (tumor suppressors), the activation of positive acting factors (oncogenes), or when chimeric proteins result from chromosomal translocations, is likely a key event in multistep tumorigenesis. Here, using the transcription factors E2F and AML-1 as model systems, we discuss the disruption of coordinate transcriptional regulation in oncogenesis. E2F oncogenic signals are released when the pRb tumor suppressor is inactivated, and E2F activation may necessitate the coordinate inactivation of a second tumor suppressor, p53. AML-1 is the target of the (8;21) translocation, found in approximately 15&#37; of acute myeloid leukemia (AML) cases, and the t(12;21), found in up to 30&#37; of childhood B-cell acute lymphoblastic leukemias. The t(8;21) creates a fusion protein between AML-1 and a gene of unknown function, <i>mtg8 (ETO)</i>, whereas the t(12:21) fuses the <i>TEL</i> (translocation-ets-leukemia) transcription factor to the N-terminus of AML-1. The inv(16), which is the most frequent anomaly found in AML, also targets AML-1, by fusing the gene that encodes AML-l's heterodimeric partner CBF&#946; to the smooth muscle myosin heavy chain gene <i>MYH11</i>. Thus, E2F and AML-1 provide excellent models for the disruption of transcriptional regulation in cancer.
PB Begell House
LK https://www.dl.begellhouse.com/journals/6dbf508d3b17c437,1bf924415e55094a,3b024ef834e0fe49.html