Disease relevance of BRD8

• Efficacy of p120 antisense-mediated therapy for pancreatic cancer [1].

High impact information on BRD8

• SMAP2 colocalized with the adaptor proteins for clathrin AP-1 and EpsinR on the early endosomes/trans-Golgi-network (TGN) [2].
• SMAP2, a novel ARF GTPase-activating protein, interacts with clathrin and clathrin assembly protein and functions on the AP-1-positive early endosome/trans-Golgi network [2].
• In addition, CREB-binding protein synergizes with p120 to enhance this effect [3].
• Thus, p120 satisfies a number of important criteria as a nuclear receptor coactivator [3].
• Cotransfection assays in CV-1 cells demonstrate that p120 enhances TR-mediated transactivation on multiple T3 response elements in the presence of T3 [3].

Biological context of BRD8

• In conclusion, endothelial cells possess protein kinase C-dependent and -independent pathways regulating p120/p100 serine/threonine phosphorylation [4].
• High resolution crystal structures of the p120 RasGAP SH3 domain [5].
• p120 antisense oligodeoxynucleotides were used to determine whether they inhibited cell growth of MIA PaCa-2, a highly tumorigenic human pancreatic carcinoma cell line [1].
• CONCLUSION: These observations suggest that rat p120 is strongly induced in the ovarian granulosa cells, and may work together with PR in the granulosa cells of ovulatory follicles to promote the ovulation process [6].

Anatomical context of BRD8

• Dephosphorylation of the catenins p120 and p100 in endothelial cells in response to inflammatory stimuli [4].
• Strong expression of p120 mRNA was observed in the granulosa cells of pre-ovulatory large antral follicles [6].

Associations of BRD8 with chemical compounds

• Interaction studies demonstrate that p120 interacts with the TR AF-2 domain in the presence of ligand through a 111-amino acid region [3].
• p120 was originally isolated as a novel nuclear co-activator for thyroid hormone receptor [7].
• In the glutathione-S-transferase pull-down assay, while steroid receptor coactivator-1 showed apparent interactions with both RXR and PPARgamma, p120 bound only to RXR in a 9-cis-retinoic acid (RA)-dependent manner and also did not bind to PPARgamma even in the presence of thiazolidinediones [7].
• Activation of receptors for agents such as histamine (H1), thrombin and lysophosphatidic acid in the endothelial cells also caused serine/threonine dephosphorylation of p120 and p100, suggesting physiological relevance [4].

Analytical, diagnostic and therapeutic context of BRD8

• The yeast two-hybrid analysis showed no interaction of p120 with PPARgamma under any conditions, and electophoretic mobility shift assay showed apparent DNA-PPARgamma/RXR/p120 complex formation only in the presence of 9-cis-RA [7].
• Seven of the eight control animals formed tumors that had a volume greater than 1200 mm3 45 days after treatment was begun, whereas only three of eight p120 antisense-treated animals had tumors that were this large [1].
• Fifteen days after the beginning of treatment, control animals had a significantly greater (P=0.0035) tumor volume (425=244 mm3 above baseline) as compared to p120 antisense-treated animals (166+/-116 mm3) [1].
• Tissue localization of p120 was examined by in situ hybridization [6].
• METHODS: A full-length cDNA encoding rat p120 was cloned, and expression of the gene in the ovary was examined by Northern blotting [6].

References