Disease relevance of Mxi1

• Mxi1-0, an alternatively transcribed Mxi1 isoform, is overexpressed in glioblastomas [1].
• Mice deficient for Mxi1 exhibit significant prostate hyperplasia [2].
• CONCLUSIONS: The ability of AdMxi1 to suppress prostate tumor cell proliferation supports a role for Mxi1 loss in the pathogenesis of a subset of human prostate cancers [2].
• METHODS: We infected DU145 prostate carcinoma cells with an Mxi1-expressing adenovirus (AdMxi1) in vitro, and measured Mxi1 expression, cell proliferation, soft agar colony formation, and cell cycle distribution [2].
• Such characterization is particularly relevant because mxi1 is lost or mutated in some human prostate tumors and mouse mxi1-null mutants show prostatic hyperplasia [3].

High impact information on Mxi1

• Our data support the view that the opposing biological actions of Myc and Mxi1 extend beyond reciprocal regulation of common gene targets [4].
• Analysis of mouse mxi1 has led to the identification of two mxi1 transcript forms possessing open reading frames that differ in their capacity to encode a short amino-terminal alpha-helical domain [5].
• Our results show that Mxi1 is involved in the homeostasis of differentiated organ systems, acts as a tumour suppressor in vivo, and engages the Myc network in a functionally relevant manner [6].
• This cancer-prone phenotype may correlate with the enhanced ability of several mxi1-deficient cell types, including prostatic epithelium, to proliferate [6].
• Consistent with these roles, mxi1 may be the tumour-suppressor gene that resides at region 24-26 of the long arm of chromosome 10 [6].

Biological context of Mxi1

• Repression was independent of Mxi1 binding to mSin3 but dependent on the Mxi1 LZ and COOH-terminal sequences, including putative casein kinase II phosphorylation sites [7].
• Human chromosomes 2p13 and 10q25 have been involved in specific tumors where the role of Mad and Mxi1 can now be investigated [8].
• Mxi1 also appears to lack a transcriptional activation domain [8].
• Therefore, Mxi1 and Mad might antagonize Myc function and are candidate tumor suppressor genes [8].
• Mxi1 is a c-Myc antagonist and suppresses cell proliferation in vitro [1].

Anatomical context of Mxi1

• Mmipl is found in a variety of cells types, is induced by serum stimulation, and can be co-immunoprecipitated from fibroblasts in association with Mxi1 [9].
• Mnt is a Max-interacting protein that can antagonize the activities of Myc oncoproteins in cultured cells [10].
• The mxi1 mRNA increased during growth inhibition and differentiation, and decreased with serum stimulation in mammal cell lines [11].
• We have used real-time PCR to confirm the changes in levels of transcripts such as renin-1, Kruppel-like factor 4, Mad4 (max-interacting protein repressor), Nur-related protein 1, and hairy/enhancer of splits gene 1 that were found to be regulated by FSH in testes of hpg mice [12].

Other interactions of Mxi1

• Mxi1 is a repressor of the c-Myc promoter and reverses activation by USF [7].
• Compensatory increases in Mxi1 and Mad3 transcripts, similar to those previously described in Mad1 null hematopoietic cells, were also seen [13].
• Here, we sought to characterize more fully the physical properties of the second homologue, mSin3A and to determine whether the recruitment of mSin3A by Mxi1 is indeed required for anti-Myc activity [14].
• Mnt: a novel Max-interacting protein and Myc antagonist [15].

Analytical, diagnostic and therapeutic context of Mxi1

• We report here the mapping of the MAD and MXI1 genes in human and mouse by fluorescence in situ hybridization (FISH) and by recombination mapping [8].

References