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changes in protein profiles in bortezomib applied multiple myeloma ...

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Spot 4, Ubiquit<strong>in</strong>-conjugat<strong>in</strong>g enzyme E2C accepts ubiquit<strong>in</strong> from the E1<br />

complex and catalyzes its covalent attachment to other prote<strong>in</strong>s. It catalyzes 'Lys-11'-<br />

and 'Lys-48'-l<strong>in</strong>ked polyubiquit<strong>in</strong>ation <strong>in</strong> vitro. Morover this prote<strong>in</strong> acts as an essential<br />

factor of the anaphase promot<strong>in</strong>g complex/cyclosome (APC/C), a cell cycle-regulated<br />

ubiquit<strong>in</strong> ligase that controls progression through mitosis. Acts by <strong>in</strong>itiat<strong>in</strong>g 'Lys-11'-<br />

l<strong>in</strong>ked polyubiquit<strong>in</strong> cha<strong>in</strong>s on APC/C substrates, lead<strong>in</strong>g to the degradation of APC/C<br />

substrates by the proteasome and promot<strong>in</strong>g mitotic exit. As this prote<strong>in</strong> is responsible<br />

for controll<strong>in</strong>g progression and has a role <strong>in</strong> prote<strong>in</strong> ubiquit<strong>in</strong>ation, its expression level<br />

is <strong>in</strong>creas<strong>in</strong>g with the Bortezomib effect.<br />

Spot 34, Ras-related prote<strong>in</strong> Rab-25 is <strong>in</strong>volved <strong>in</strong> the regulation of cell survival.<br />

Similar to spot 2, 4, and 18, its expression degree <strong>in</strong>creases <strong>in</strong> response to Bortezomib.<br />

Spot 5, Paxill<strong>in</strong> is a cytoskeletal prote<strong>in</strong> <strong>in</strong>volved <strong>in</strong> act<strong>in</strong>-membrane attachment<br />

at sites of cell adhesion to the extracellular matrix (focal adhesion). With the apply<strong>in</strong>g<br />

anticancer agents to the cells, it was lost.<br />

Spot 14, Signal<strong>in</strong>g trashold-regulat<strong>in</strong>g transmembrane adapter 1 negatively<br />

regulates TCR (T-cell antigen receptor)-mediated signal<strong>in</strong>g <strong>in</strong> T-cells. It is also <strong>in</strong>volved<br />

<strong>in</strong> positive selection of T-cells. It is specifically expressed <strong>in</strong> T and B-cells and present<br />

<strong>in</strong> plasma cells but not <strong>in</strong> germ<strong>in</strong>al center B-cells (at prote<strong>in</strong> level). Furthermore, it is<br />

expressed <strong>in</strong> T- and B-cell lymphoma. Like spot 5, it was lost with the Bortezomib.<br />

Spot 15, Caspase recruitment doma<strong>in</strong>-conta<strong>in</strong><strong>in</strong>g prote<strong>in</strong> 14 activates NF-κB via<br />

BCL10 and IKK and stimulates the phosphorylation of BCL10. The ma<strong>in</strong> goal of<br />

Bortezomib is <strong>in</strong>hibit the proteasomes for prevent<strong>in</strong>g the IκB degredation and<br />

accord<strong>in</strong>gly NF-κB activation, so it is very required to lose of this prote<strong>in</strong> as expected.<br />

Spot 23, NF-κB <strong>in</strong>hibitor delta may regulate the expression of IL-2, IL-6, and<br />

other cytok<strong>in</strong>es through regulation on NF-κB activity, similarly to spot 15.<br />

Spot 6, Glutathione peroxidase 3 protects cells and enzymes from oxidative<br />

damage, by catalyz<strong>in</strong>g the reduction of hydrogen peroxide, lipid peroxides and organic<br />

hydroperoxide, by glutathione. So, it is an example of newly formed prote<strong>in</strong> after the<br />

Bortezomib effects upon MM U-266 cells.<br />

For spot 7, we obta<strong>in</strong>ed two prote<strong>in</strong>s that have the change to be the correct one<br />

after the mass spectrometric analysis. One of them was Mitogen-activated prote<strong>in</strong><br />

k<strong>in</strong>ase k<strong>in</strong>ase k<strong>in</strong>ase k<strong>in</strong>ase 1 which may play a role <strong>in</strong> the response to environmental<br />

stress. This prote<strong>in</strong> appears to act upstream of the JUN N-term<strong>in</strong>al pathway and might<br />

play a role <strong>in</strong> hematopoietic l<strong>in</strong>eage decisions and growth regulation. As well as, it is<br />

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