Lap report Lab Example | Topics and Well Written Essays - 2500 words

Lap - Lab Report Example Apart from playing an important role in the maintenance of homeostasis in a constantly regenerating population of cells, such as the colonic epithelium, apoptosis also functions to destroy cells with DNA damage and prevent neoplasia. Inhibitor of apoptosis or IAP proteins are a class of anti-apoptotic regulator proteins which are characterized by the presence of baculoviral IAP repeat (BIR) domains. IAPs inhibit the activation caspases which are the key effector proteases of apoptosis, by directly binding to them through the BIR domains. Extensive evidence exists to show the involvement of the IAP family of proteins in oncogenesis, via their efficient suppression of apoptosis (Hunter et al., 2007). Survivin is a novel member of the IAP family of proteins with a potential dual role in apoptosis inhibition and regulation of mitosis. Survivin inhibits apoptosis by interfering with the function of caspase-3, caspase-7 and caspase-9 (Shin et al., 2001; Dohi et al., 2004). In addition to a poptosis inhibition, survivin is implicated in the regulation of the mitotic spindle checkpoint and the promotion of angiogenesis, and chemoresistance (Altieri, 2003; Mita et al., 2008). Several mitotic kinases, including the three Aurora kinases, Aurora-A, -B and –C kinases regulate the progression of the cell through mitosis. Lens et al. (2006) have provided evidence to show that survivin acts as a mitotic regulator. It functions as a subunit of the chromosomal passenger complex, which is essential for proper chromosome segregation and cytokinesis. In this complex, Aurora B acts as the enzymatic core, while survivin dictates chromosomal passenger complex localization. Survivin is uniquely placed at the border of both the cell-death machinery and mechanisms of cell cycle progression and microtubule stability (Dan et al., 2004). Survivin is a highly conserved 16.5Â  kDa protein with 142 amino acids. X-ray crystallography has revealed the protein to be an unusual bow tie-shap ed dimer with two ?-helical extensions (Chantalat et al., 2000). It interacts with the microtubules through the ?-helical extension at the carboxyl terminal. Expressed in the G2/M phase (Li et al., 1998), survivin is up-regulated in almost all cancers, including colon cancer, but has low or no expression in most normal, differentiated adult tissues (Duffy et al., 2007). Expression of survivin in cancer cells has been shown to promote tumorigenesis (Li, 2005), cancer progression, poor prognosis, shortened patient survival and resistance to chemo- and radiation therapies (Li and Ling, 2006). A number of signaling molecules, transcription factors and other ligands modulate survivin expression and/or function in cancer cells through transcriptional and/or posttranscriptional mechanisms (Zhang et al., 2006). Of these, regulation of its gene transcription is an important mechanism for the modulation of survivin expression. Sp1, a transcription factor is reported to be involved in the tran scriptional activation of survivin (Li and Altieri, 1999). According to Kim et al. (2003), an aberrant TCF/? catenin might cause the stimulation of survivin expression leading to enhanced cell proliferation and resistance to apoptosis, thereby promoting the molecular pathogenesis of colorectal cancer. Zhang et al. (2000) demonstrated that APC mutation causes