Our earlier work, has shown that post translational modifications of TCTP such as proteoly sis and dimerization are prerequisites that endow TCTP with its plethora of functions. TCTP unless is significantly overexpressed in tumor cells while suppression of TCTP expression enhances apoptosis and causes reversion of transformed cells to their normal phenotype. Inhibitors,Modulators,Libraries TCTP exhibits its anti apoptotic func tions through mechanisms that stabilize the anti apoptotic Bcl 2 family protein, MCL1 and that antagonize the dimerization of pro apoptotic Bax. The N terminal region of TCTP is known to be involved in the antiapoptotic mechanism via interaction with antiapop totic Bcl xL. As a Ca2 binding protein, TCTP seques ters the intracellular Ca2 to perturb the Ca2 dependent apoptosis.

In addition, recent reports suggest Inhibitors,Modulators,Libraries that TCTP represses the tumor suppressor p53 in a reciprocal mode. We recently showed that Na,K ATPase, an interacting partner in tumorigenesis, directly asso ciates with TCTP to induce human breast epithelial cell transformation through Src dependent EGFR transac tivation. Also, it has been reported that TCTP overexpression induces chemoresistance by protecting the various tumor cells against DNA damaging agents such as etoposide or 5 fluorouracil and against tunicamycin induced endoplas mic reticulum stress. Of interest, increased expression of TCTP is revealed to have an interrelation with increased chemoresistance, of malignant melanoma to cytotoxic agents such as etoposide and its increased survival. In addition, a temporal proteome profiling upon taxol exposure, revealed increased TCTP expression during apoptosis.

Studies of colon cancer cell re sponse to oxaliplatin treatment revealed temporal upregu lation of TCTP. However, little is known about the unique molecular mechanisms in the role of TCTP in Inhibitors,Modulators,Libraries the development of the chemoresistance of tumor cells against anticancer drugs such as etoposide, taxol, Inhibitors,Modulators,Libraries and oxaliplatin. In this context, the role of deregulation or defects of apoptosome function in the development of chemoresis tance, needs consideration as most anticancer drugs suggested to mediate cell death via mitochondrial apop totic pathway. For example, inactivation or silencing of apoptotic protease activating factor, has been implicated in the development of chemoresistance by metastatic malignant melanomas.

Inhibition of Apaf 1 provides a Inhibitors,Modulators,Libraries preferential survival advantage to neo plastic selleck chemicals llc cells and the lack of cytosolic Apaf 1 due to its sequestration in lipid raft is noted as a new mechan ism of chemoresistance in B lymphoma. Acquired cisplatin resistance is partially reversed when Apaf 1 is exogenously overexpressed in HeLa cells. Further more, it has been shown that apoptosome dependent apoptosis can be inhibited when Apaf 1 is exposed to endogenous regulators including Bcl xL, Heat shock protein 70, and Apaf 1 interacting protein.