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gene was interrupted at a position 3.6
kb downstream of exon 13, inverted, and ligated approximately 300
bp upstream of
particular specimen, the
EML4
successfully amplified
this genome fragment containing the fusion point between the
ALK
exon 20 [9]. Soda
et al.
EML4
and
ALK
genes, proving the presence of inv(2)(p21p23) in the cancer
cells.
Figure 16.1
Both the ALK gene and the EML4 gene map to chromosome 2p,
but have opposite orientations [9]).
16.2.1
The Structure and Function of EML4
Microtubules switch between growing and shrinking phases. These
dynamic structures are regulated by microtubule-associated proteins
(MAPs) [12]. The most abundant MAP in dividing sea urchin eggs is
the echinoderm microtubule-associated protein (EMAP) [13]. There
are at least five mammalian homologues of EMAP, or EMLs (EMAP-
like proteins), that have been identified. These EMLs share two
unique domains that are highly conserved: the hydrophobic EMAP
like (HELP) domain near the amino-terminal portion and multiple
WD40 domains within the carboxy-terminal portion.
encodes a 120 kDa EML that has been shown to bind
polymerized microtubules
EML4
[12]. The function of EML4 is
likely regulated by differential phosphorylation of serine/threonine
residues during the cell cycle. Studies have shown that ELM4 is
essential for microtubule formation and stabilization during mitosis
[13]. Silencing the gene results in a significant reduction of the
proliferation rate of HeLe cells
in vitro
in vitro
and
EML4
-negative cells
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