## 1 Introduction  
Survivin (baculoviral inhibitor of apoptosis repeat-containing 5, BIRC5) is the smallest member of the inhibitor of apoptosis (IAP) protein family [1]. It is coded by the BIRC5 gene and its molecular weight is 16.5 kDa. Survivin is overexpressed in many cancers, e.g., head-and-neck squamous cell carcinoma [2], ovarian [3] or gastric tumors [4], and hematologic malignancies [5], and its overexpression is associated with poor prognosis. On the other hand, survivin is almost undetectable in differentiated healthy cells, making it a promising target for cancer therapy [6]. Survivin has at least two independent functions [7]. It controls centrosome-microtubule assessment and microtubule-mediated sister chromatid separation during mitosis, and it plays an important role in apoptosis, in which it mediates inhibition of executive caspase \(3/7\) activity [8]. The two distinct functions of survivin determine its variable localization. In mitotic cells, survivin forms complexes with other chromosome passenger complex-related proteins, Borealin and Aurora B, and it localizes at kinetochores in metaphase, at midzone in anaphase, and at the chromatin bridge in telophase. The C-terminal part of the survivin molecule was found to be responsible for the proper localization of survivin during mitosis [9]. Conversely, the N-terminus is required for apoptosis induced by irradiation [9] and relocalization of survivin from the cytoplasm to the nuclei was observed during apoptosis [10]. The survivin promoter is directly regulated by tumor suppressor p53, and survivin overexpression is frequently detected in p53-deficient cells [11, 12]. Drug-induced stabilization of p53 protein often leads to survivin deregulation [8; 13; 14; 15]. Interestingly, p53/nuclear factor (NF)-xB crosstalk during replication stress enhances survivin level and chemoresistance [16]. Survivin silencing induced p21 and p53 expression in breast carcinoma cells [17]. p21-mediated survivin suppression at the transcription level was found in HepG2 cells, likely through the block at gap 1 (G1)/G0 phase and downregulation of transcription factors E2F-1 and p300 [18]. Conversely, survivin binds Cdk4 from complex with p21, which releases the p21 for an interaction with proaspase 3 and blocks caspase-3 activity [19]. However, p21-induced survivin attenuation was observed only in cells arrested in G1/G0 phase, while enhanced survivin level was detected when p21 overexpression occurred during synthesis (S)-G2 transition [20]. Survivin expression is also regulated by transcription factors STAT3 and 5 [21; 22] or \(\beta\)-catenin [12; 23], which are important downstream molecules of fms-like tyrosine kinase 3 (Flt3) signalization [24]. Survivin interacts also with other members of the IAP family, particularly with X-linked inhibitor of apoptosis (XIAP). Cytoplasmic survivin stabilizes XIAP and enhances its antiapoptotic function [25]. Recently, it was reported that survivin overexpression in leukemia stem cells (LSCs), together with XIAP overexpression in granulocytes, causes a resistance of chronic myeloid leukemia (CML) cells to treatment with imatinib [26]. Survivin interaction with XIAP results in lower activity of caspase 9 [8]. On the other hand, survivin degradation in the proteasome is regulated by XIAP-mediated ubiquitinylation [16]. Survivin also contributes to DNA damage repair [17; 27]. Moreover, it was reported to affect cell adhesivity [28] or intercellular communication [29]. Several studies reported on the positive correlation of high survivin expression with worse survival and relapse-free prognosis in various cancer types [30; 31; 32]. Low survivin expression was also correlated with statistically significant prolonged overall survival in a group of acute myeloid leukemia (AML) patients [33]. However, survivin expression in AML is heterogeneous and different transcription variants were reported to correlate with prognosis in various patient subsets.