Balliet Arthur G, Hollander M Christine, Fornace Albert J, Hoffman Barbara, Liebermann Dan A
Fels Institute for Cancer Research and Molecular Biology and the Department of Biochemistry, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA.
DNA Cell Biol. 2003 Jul;22(7):457-68. doi: 10.1089/104454903322247334.
Gadd45g/CR6, Gadd45b/MyD118, and Gadd45a/Gadd45 are members of a gene family that displays distinct patterns of gene expression in response to stimuli that induce differentiation, growth arrest, and/or apoptosis. All three of these highly conserved proteins interact with a number of critical cell cycle and cell survival regulatory proteins such as PCNA, p21(WAF1/CIP1), CDK1 (cdc2-p34), and MTK1/MEKK4, and have been reported to influence the activity of the p38 and JNK kinases. Species-blot analysis showed that Gadd45g is an evolutionarily conserved gene and sequence analysis showed that Gadd45g has a gene structure conserved with that of other members of its gene family. A comparison of the putative transcription factor binding sites found in the sequences of the gene family members suggests, that like Gadd45b, NF-kappaB and STATs may be responsible for the differences in regulation of expression observed between Gadd45g and Gadd45a. Analysis of the Gadd45b/MyD118 promoter shows that there are three different enhanceosome-like regions that may allow cell-type specific responses to TGF-beta1 by the Gadd45b/MyD118 promoter. Fluorescent in situ hybridization (FISH) confirmed the localization of the Gadd45g gene to mouse chromosome band 13A5-B, which has been reported to contain a quantitative trait locus that regulates body weight in mice. This suggests that alleles of the Gadd45g gene may function in the regulation of body weight, in addition to its currently recognized roles in differentiation and stress responses.
Gadd45g/CR6、Gadd45b/MyD118和Gadd45a/Gadd45是一个基因家族的成员，该家族在对诱导分化、生长停滞和/或凋亡的刺激作出反应时表现出不同的基因表达模式。这三种高度保守的蛋白质都与许多关键的细胞周期和细胞存活调节蛋白相互作用，如增殖细胞核抗原（PCNA）、p21（WAF1/CIP1）、周期蛋白依赖性激酶1（CDK1，即cdc2-p34）和丝裂原激活的蛋白激酶激酶激酶1/丝裂原激活的蛋白激酶激酶4（MTK1/MEKK4），并且据报道会影响p38和JNK激酶的活性。种系杂交分析表明，Gadd45g是一个进化上保守的基因，序列分析表明，Gadd45g具有与其基因家族其他成员保守的基因结构。对该基因家族成员序列中推定的转录因子结合位点进行比较表明，与Gadd45b一样，核因子κB（NF-κB）和信号转导子与转录激活子（STATs）可能是导致Gadd45g和Gadd45a之间观察到的表达调控差异的原因。对Gadd45b/MyD118启动子的分析表明，存在三个不同的增强体样区域，它们可能使Gadd45b/MyD118启动子对转化生长因子-β1（TGF-β1）产生细胞类型特异性反应。荧光原位杂交（FISH）证实了Gadd45g基因定位于小鼠染色体带13A5-B，据报道该区域包含一个调节小鼠体重的数量性状基因座。这表明，Gadd45g基因的等位基因除了在分化和应激反应中目前已被认识的作用外，可能还在体重调节中发挥作用。
