TY - JOUR
T1 - Trim24 (Tif1a)
T2 - An essential 'brake' for retinoic acid-induced transcription to prevent liver cancer
AU - Khetchoumian, Konstantin
AU - Teletin, Marius
AU - Tisserand, Johan
AU - Herquel, Benjamin
AU - Ouararhni, Khalid
AU - Losson, Régine
PY - 2008/12/1
Y1 - 2008/12/1
N2 - Retinoic acid (RA), the active derivative of vitamin A, is an important signaling molecule that controls various developmental processes and influence the proliferation and differentiation of a variety of cell types. RA exerts its biological functions primarily through binding to and activating nuclear RA receptors (RARs, which include the RARa, b and g isotypes RARA, RARB and RARC). Aberrant expression or impaired function of these nuclear receptors has been linked to diverse types of cancer. RARs are RA-dependent transcription factors that regulate gene expression through the recruitment of different co-regulators (co-activators and co-repressors). TRIM24 (formerly known as TIF1α) was among the first co-regulators identified as interacting with RARs in a ligand-dependent fashion, and it was recently shown to function in mice as a potent liver-specific tumor suppressor by attenuating Rara-mediated transcription. The fact that Trim24-/-, but not Trim24 -/-Rara+/-, mutant mice are highly predisposed to the development of hepatocellular carcinoma (HCC) has significant implications in cancer research. This result, along with the observation that in response to pharmacological inhibition of the RA signaling, hepatocytes lacking Trim24 loose their ability to proliferate, strongly implicates Rara as a proto-oncogene in hepatocytes and demonstrates that overactivated RA signaling is deleterious to liver homeostasis.
AB - Retinoic acid (RA), the active derivative of vitamin A, is an important signaling molecule that controls various developmental processes and influence the proliferation and differentiation of a variety of cell types. RA exerts its biological functions primarily through binding to and activating nuclear RA receptors (RARs, which include the RARa, b and g isotypes RARA, RARB and RARC). Aberrant expression or impaired function of these nuclear receptors has been linked to diverse types of cancer. RARs are RA-dependent transcription factors that regulate gene expression through the recruitment of different co-regulators (co-activators and co-repressors). TRIM24 (formerly known as TIF1α) was among the first co-regulators identified as interacting with RARs in a ligand-dependent fashion, and it was recently shown to function in mice as a potent liver-specific tumor suppressor by attenuating Rara-mediated transcription. The fact that Trim24-/-, but not Trim24 -/-Rara+/-, mutant mice are highly predisposed to the development of hepatocellular carcinoma (HCC) has significant implications in cancer research. This result, along with the observation that in response to pharmacological inhibition of the RA signaling, hepatocytes lacking Trim24 loose their ability to proliferate, strongly implicates Rara as a proto-oncogene in hepatocytes and demonstrates that overactivated RA signaling is deleterious to liver homeostasis.
KW - Hepatocarcinogenesis
KW - Knockout
KW - Mouse model
KW - Proliferation
KW - Quiescence
KW - Retinoic acid receptor alpha
KW - TRIM24/TIF1α
KW - Transcriptional repression
UR - http://www.scopus.com/inward/record.url?scp=57349132931&partnerID=8YFLogxK
U2 - 10.4161/cc.7.23.7123
DO - 10.4161/cc.7.23.7123
M3 - Review article
C2 - 19029830
AN - SCOPUS:57349132931
SN - 1538-4101
VL - 7
SP - 3647
EP - 3652
JO - Cell Cycle
JF - Cell Cycle
IS - 23
ER -