TY - JOUR
T1 - REST in good times and bad
T2 - Roles in tumor suppressor and oncogenic activities
AU - Majumder, Sadhan
N1 - Funding Information:
I would like to thank Marcus Curl, Mohamedi Kagalwala, and Mary Majumder for help with the manuscript and the National Institutes of Health for funding (grants CA97124 and CA81255).
PY - 2006/9/1
Y1 - 2006/9/1
N2 - The repressor element 1 (RE-1)-silencing transcription factor (REST), also known as the neuron-restrictive silencer factor (NRSF), was originally discovered as a transcriptional repressor of a large number of primarily terminal neuronal differentiation genes in non-neuronal cells and neural stem cells (NSCs). Although REST is expressed in NSCs, its transcription is generally blocked as NSCs undergo differentiation, and it is rarely expressed in terminally differentiated neurons. In support of its function as a transcriptional repressor, REST was found to contain a DNA-binding domain and two repressor domains. The repressor domains were found to associate, directly or indirectly, with a large number of cellular repressor complexes. Thus, REST was considered a major epigenetic regulator controlling chromatin modification. However, REST is expressed in some differentiated neurons, and when bound to a double-stranded small RNA, REST was later found to also function as an activator of its same target neuronal differentiation genes in NSCs. In addition, REST has been found to regulate an evolving array of genes and cellular functions, making it a biological enigma. For example, REST was recently found to have a seemingly paradoxical role in both tumor suppressor activity and oncogenic activity. Current evidence suggests that the diverse cellular context generated by intrinsic factors in the cell, the amount of REST protein present in the cell, the affinity of the REST protein for its specific target gene, and the cellular niche dictate such behavior.
AB - The repressor element 1 (RE-1)-silencing transcription factor (REST), also known as the neuron-restrictive silencer factor (NRSF), was originally discovered as a transcriptional repressor of a large number of primarily terminal neuronal differentiation genes in non-neuronal cells and neural stem cells (NSCs). Although REST is expressed in NSCs, its transcription is generally blocked as NSCs undergo differentiation, and it is rarely expressed in terminally differentiated neurons. In support of its function as a transcriptional repressor, REST was found to contain a DNA-binding domain and two repressor domains. The repressor domains were found to associate, directly or indirectly, with a large number of cellular repressor complexes. Thus, REST was considered a major epigenetic regulator controlling chromatin modification. However, REST is expressed in some differentiated neurons, and when bound to a double-stranded small RNA, REST was later found to also function as an activator of its same target neuronal differentiation genes in NSCs. In addition, REST has been found to regulate an evolving array of genes and cellular functions, making it a biological enigma. For example, REST was recently found to have a seemingly paradoxical role in both tumor suppressor activity and oncogenic activity. Current evidence suggests that the diverse cellular context generated by intrinsic factors in the cell, the amount of REST protein present in the cell, the affinity of the REST protein for its specific target gene, and the cellular niche dictate such behavior.
KW - Breast cancer
KW - Chromatin
KW - Colon cancer
KW - Epigenetic regulation
KW - Lung cancer
KW - Medulloblastoma
KW - Neuronal differentiation
KW - Oncogenic activity
KW - REST/NRSF
KW - Tumor-suppressor activity
UR - http://www.scopus.com/inward/record.url?scp=33748921564&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33748921564&partnerID=8YFLogxK
U2 - 10.4161/cc.5.17.2982
DO - 10.4161/cc.5.17.2982
M3 - Review article
C2 - 16929174
AN - SCOPUS:33748921564
SN - 1538-4101
VL - 5
SP - 1929
EP - 1935
JO - Cell Cycle
JF - Cell Cycle
IS - 17
ER -