Disease relevance of MAPRE1

• MLL is fused to EB1 (MAPRE1), which encodes a microtubule-associated protein, in a patient with acute lymphoblastic leukemia [1].
• Both Epstein-Barr virus (EBV)-encoded trans-acting factors, EB1 and EB2, are required to activate transcription from an EBV early promoter [2].
• The evolutionarily conserved protein EB1 originally was identified by its physical association with the carboxyl-terminal portion of the adenomatous polyposis coli (APC) tumor suppressor protein, an APC domain commonly mutated in familial and sporadic forms of colorectal neoplasia [3].
• Immunofluorescence analysis of SW480, a colon cancer cell line that expresses only carboxyl-terminal-deleted APC unable to interact with EB1, demonstrated that EB1 remained localized to the microtubule cytoskeleton, suggesting that this pattern of subcellular distribution is not mediated by its interaction with APC [3].
• The Raji, EB1, and EB2 cell lines are derived from Epstein-Barr virus (EBV)-positive Burkitt's lymphomas [4].

High impact information on MAPRE1

• Furthermore, myosin X and the microtubule plus-end-tracking protein EB1 are shown to play a role in this mechanism through remodeling of actin cytoskeleton and stabilization of astral microtubules, respectively [5].
• Integrin-mediated adhesion orients the spindle parallel to the substratum in an EB1- and myosin X-dependent manner [5].
• Phosphorylation of the conserved Cdc2 site Ser2789-Lys2792 in C-APCp1 reduces binding four-fold, indicating that the interaction APC-EB1 is post-translationally regulated in cells [6].
• Our results demonstrate that EB1 is a novel component of the microtubule cytoskeleton in mammalian cells [3].
• The subcellular localization of EB1 in epithelial cells was studied by using immunofluorescence and biochemical techniques [3].

Chemical compound and disease context of MAPRE1

• Although Hafnia alvei was a major component of the Enterobacteriaceae flora in all foods tested and a strong AHL producer, the signal molecules produced by H. alvei strain EB1 did not influence protease production by Pseudomonas fluorescens strain 395 in vitro [7].

Biological context of MAPRE1

• We found that the three MAPRE genes had similar genomic structures but were on different chromosomes [8].
• EB1 colocalized both to cytoplasmic microtubules in interphase cells and to spindle microtubules during mitosis, with pronounced centrosome staining [3].
• Mlph is proposed to be a modular protein binding the melanosome-associated protein Rab27a, Myosin Va (MyoVa), actin, and microtubule end-binding protein (EB1), via distinct N-terminal Rab27a-binding domain (R27BD), medial MyoVa-binding domain (MBD), and C-terminal actin-binding domain (ABD), respectively [9].
• Immunohistochemical analyses reveal a distinct staining pattern during interphase as well as an association of RP1/EB1 with mitotic microtubule structures [10].
• Monoclonal antibody EB1 has been shown to enhance the actions of hGH on growth and body composition in Snell dwarf mice and to increase food conversion efficiency [11].

Anatomical context of MAPRE1

• The dynamic behavior of the APC-binding protein EB1 on the distal ends of microtubules [12].
• On the other hand, when microtubules were disassembled by nocodazole, EB1 was not co-localized with APC-GFP, which was concentrated along the basal plasma membrane [12].
• Associating with the mitotic apparatus, EB1 may play a physiologic role connecting APC to cellular division, coordinating the control of normal growth and differentiation processes in the colonic epithelium [3].
• The cytoskeletal array detected by anti-EB1 antibody was abolished by incubation of the cells with nocodazole, an agent that disrupts microtubules; upon drug removal, EB1 localized to the microtubule-organizing center [3].
• Other regions of Mlph reported to interact with MyoVa globular tail, actin, or EB1 are not essential for melanosome transport rescue [9].

Associations of MAPRE1 with chemical compounds

• Recruitment of EB1 to microtubules required Ca(2+) influx, but was independent of PKC [13].
• Inclusion of 3-nitro-l-tyrosine (NO(2)Tyr) in the culture medium resulted in the selective nitrotyrosination of alpha-tubulin, that was paralleled by decreased elaboration of Glu-tubulin, decreased expression of cyclins A and E, decreased association of the microtubule plus-end binding protein EB1, and inhibited cell proliferation [14].

Physical interactions of MAPRE1

• Pin2/TRF1 bound EB1 both in vitro and in vivo and they also co-localize at the mitotic spindle in cells [15].
• CLIP-170 interacts with dynactin complex and the APC-binding protein EB1 by different mechanisms [16].

Co-localisations of MAPRE1

• Therefore, EB1 appeared to be co-localized and interact with APC on the growing ends of a subset of microtubules [12].

Regulatory relationships of MAPRE1

• Furthermore, EB1 inhibits the ability of Pin2/TRF1 to promote microtubule polymerization in vitro [15].

Other interactions of MAPRE1

• The MAPRE genes encode the EB1 family proteins [8].
• Here we characterized a new Pin2/TRF1-interacting protein, EB1, that was originally identified in our yeast two-hybrid screen [15].
• These findings showed that the APC-EB1 interaction is regulated within cells and is allowed near the ends of microtubules only under restricted conditions [12].
• CLIP-170 localizes dynamically to growing microtubule plus ends, colocalizing with the dynein activator dynactin and the APC-binding protein EB1 [16].
• The elongation speed measured using the GFP-tagged end-binding protein-1 exceeded 200 nm/s and was not influenced by MAP-4 [17].

References