TY - JOUR
T1 - Integration and diversity of the regulatory network composed of Maf and CNC families of transcription factors
AU - Motohashi, Hozumi
AU - O'Connor, Tania
AU - Katsuoka, Fumiki
AU - Engel, James Douglas
AU - Yamamoto, Masayuki
N1 - Funding Information:
This work was supported in part by JSPS, CREST, PROBRAIN and the Ministry of Education, Science, Sports and Culture of Japan.
PY - 2002/7/10
Y1 - 2002/7/10
N2 - Recent progress in the analysis of transcriptional regulation has revealed the presence of an exquisite functional network comprising the Maf and Cap 'n' collar (CNC) families of regulatory proteins, many of which have been isolated. Among Maf factors, large Maf proteins are important in the regulation of embryonic development and cell differentiation, whereas small Maf proteins serve as obligatory heterodimeric partner molecules for members of the CNC family. Both Maf homodimers and CNC-small Maf heterodimers bind to the Maf recognition element (MARE). Since the MARE contains a consensus TRE sequence recognized by AP-1, Jun and Fos family members may act to compete or interfere with the function of CNC-small Maf heterodimers. Overall then, the quantitative balance of transcription factors interacting with the MARE determines its transcriptional activity. Many putative MARE-dependent target genes such as those induced by antioxidants and oxidative stress are under concerted regulation by the CNC family member Nrf2, as clearly proven by mouse germline mutagenesis. Since these genes represent a vital aspect of the cellular defense mechanism against oxidative stress, Nrf2-null mutant mice are highly sensitive to xenobiotic and oxidative insults. Deciphering the molecular basis of the regulatory network composed of Maf and CNC families of transcription factors will undoubtedly lead to a new paradigm for the cooperative function of transcription factors.
AB - Recent progress in the analysis of transcriptional regulation has revealed the presence of an exquisite functional network comprising the Maf and Cap 'n' collar (CNC) families of regulatory proteins, many of which have been isolated. Among Maf factors, large Maf proteins are important in the regulation of embryonic development and cell differentiation, whereas small Maf proteins serve as obligatory heterodimeric partner molecules for members of the CNC family. Both Maf homodimers and CNC-small Maf heterodimers bind to the Maf recognition element (MARE). Since the MARE contains a consensus TRE sequence recognized by AP-1, Jun and Fos family members may act to compete or interfere with the function of CNC-small Maf heterodimers. Overall then, the quantitative balance of transcription factors interacting with the MARE determines its transcriptional activity. Many putative MARE-dependent target genes such as those induced by antioxidants and oxidative stress are under concerted regulation by the CNC family member Nrf2, as clearly proven by mouse germline mutagenesis. Since these genes represent a vital aspect of the cellular defense mechanism against oxidative stress, Nrf2-null mutant mice are highly sensitive to xenobiotic and oxidative insults. Deciphering the molecular basis of the regulatory network composed of Maf and CNC families of transcription factors will undoubtedly lead to a new paradigm for the cooperative function of transcription factors.
KW - Antioxidant responsive element
KW - Basic region leucine zipper structure
KW - Maf recognition element
KW - Nuclear factor erythroid 2
UR - http://www.scopus.com/inward/record.url?scp=0037055265&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0037055265&partnerID=8YFLogxK
U2 - 10.1016/S0378-1119(02)00788-6
DO - 10.1016/S0378-1119(02)00788-6
M3 - Review article
C2 - 12234662
AN - SCOPUS:0037055265
VL - 294
SP - 1
EP - 12
JO - Gene
JF - Gene
SN - 0378-1119
IS - 1-2
ER -