Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Angiotensin II AT(2) receptor interacting protein 1 (ATIP1) has been recently identified as a tumor suppressor. In the present study, a 2.2 kb fragment of the 5' flanking region of the human ATIP1 gene was cloned, and its promoter activity was confirmed. Two putative p53 binding sites were identified in the minimal promoter. Cisplatin treatment and ectopic expression of p53 led to enhanced ATIP1 expression. Knockdown of p53 reduced the ATIP1 expression. The direct interaction of p53 and the ATIP1 promoter was confirmed by reporter gene and chromatin-immunoprecipitation assays. When the p53 sites were mutated, the effect of p53 on ATIP1 promoter was eliminated. The results suggest that the ATIP1 gene is regulated by p53 at the transcriptional level, and that it may play an important role in cancer initiation and progression.
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PMID:p53 regulates the expression of human angiotensin II AT(2) receptor interacting protein (ATIP1) gene. 2202 29

Microtubule-associated tumor suppressor gene (MTUS1, also known as mitochondrial tumor suppressor) is a recently identified tumor suppressor gene that has been implicated in several cancer types. The expression of MTUS1 gene leads to 5 known transcript variants and codes for 5 isoforms of Angiotensin II AT2 receptor interacting protein (ATIP). In this study, we first confirmed that the down-regulation of MTUS1/ATIP was a frequent event in oral tongue squamous cell carcinoma (OTSCC) and the premalignant lesion (leukoplakia). We further demonstrated that the down-regulation of MTUS1/ATIP was correlated with poor differentiation and enhanced proliferation (Ki67 proliferation index). Statistical analysis suggests that the down-regulation of MTUS1/ATIP was associated with reduced overall survival. Isoform specific quantitative RT-PCR assays revealed that ATIP1, ATIP3a and ATIP3b were the major isoforms of the MTUS1 gene products in oral tongue epithelial cells. Significant down-regulations were observed for all 3 ATIP isoforms in OTSCC as compared to matching normal tissues. In vitro functional study showed that the restoration of ATIP1 expression led to G1 arrest, apoptosis and reduction of cell proliferation in OTSCC cell lines. These ATIP1-induced cellular changes were accompanied by reduced phosphorylation of ERK1/2 and up-regulation of p53. Taken together, these data suggest that MTUS1 plays major roles in the progression of OTSCC, and may serve as a biomarker or therapeutic target for patients with OTSCC.
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PMID:Down-regulation of tumor suppressor MTUS1/ATIP is associated with enhanced proliferation, poor differentiation and poor prognosis in oral tongue squamous cell carcinoma. 2215 18