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Pim
The PIM kinases, which constitute a class of serine/threonine kinase, act as oncoproteins and promote cell survival by transcriptional activation of genes involved in cell proliferation. The family of PIM kinase consists of three isoforms, PIM-1, PIM-2, and PIM-3. Each of the PIM kinases plays an important role in tumorigenesis. While PIM-1 has been reported to be over-expressed in several hematological and solid tumors PIM-2 is highly expressed in myeloma, lymphoma and leukemia. The elevated expression of PIM-3 has been noted in adeno-carcinomas. Diverse roles that the PIM kinases play in carcinogenesis include multiple myeloma proliferation, anti- apoptosis, cell cycle modulation, and mediating bone destruction.
PIM kinases could inhibit apoptosis and promote cell cycle progression in prostate cancer and their overexpression relates to the grade and neoplastic transformation. The overexpression of PIM-1 in breast cancer is related to poor prognosis in HER2- and hormone-negative tumors. Thus, PIM kinases play an important role in tumorigenesis. PIM kinases are involved in downstream physiological pathways via phosphorylating many cellular substrates, for example, transcriptional modulators including myelocytomatosis (MYC); cell cycle modulators including p21Cip1/Waf1 (CDKN1A), p27KIP1 (CDKN1B), and cell division cycle 25A (CDC25A) and 25C (CDC25C); signaling intermediates such as Notch homolog, translocation-associated (Notch1); and apoptosis modulators such as BCL-2-associated agonist of cell death (BAD).
Both the PIM family and protein kinase b (PKB)/AKT family belong to the serine/threonine protein kinases family and both play important roles in cancer development.35 PIM kinases have constitutive activity, and the half-lives of their mRNA and proteins are relatively short. EPH-like tyrosine kinase (ETK) phosphorylates PIM-1 at the Thr-218 residue, and this process is involved in the interlukin (IL)-6-induced activation of androgen-mediated transcription. Furthermore, protein phosphatase 2 (PP2A) can decrease the stability of PIM kinases. PIM kinases received much attention for anticancer drug development since they have aberrantly expressed in distinct cancer types.
References
1.Xinning Zhang,et al. J Cancer Prev. 2018 Sep; 23(3): 109–116.
PIM kinases could inhibit apoptosis and promote cell cycle progression in prostate cancer and their overexpression relates to the grade and neoplastic transformation. The overexpression of PIM-1 in breast cancer is related to poor prognosis in HER2- and hormone-negative tumors. Thus, PIM kinases play an important role in tumorigenesis. PIM kinases are involved in downstream physiological pathways via phosphorylating many cellular substrates, for example, transcriptional modulators including myelocytomatosis (MYC); cell cycle modulators including p21Cip1/Waf1 (CDKN1A), p27KIP1 (CDKN1B), and cell division cycle 25A (CDC25A) and 25C (CDC25C); signaling intermediates such as Notch homolog, translocation-associated (Notch1); and apoptosis modulators such as BCL-2-associated agonist of cell death (BAD).
Both the PIM family and protein kinase b (PKB)/AKT family belong to the serine/threonine protein kinases family and both play important roles in cancer development.35 PIM kinases have constitutive activity, and the half-lives of their mRNA and proteins are relatively short. EPH-like tyrosine kinase (ETK) phosphorylates PIM-1 at the Thr-218 residue, and this process is involved in the interlukin (IL)-6-induced activation of androgen-mediated transcription. Furthermore, protein phosphatase 2 (PP2A) can decrease the stability of PIM kinases. PIM kinases received much attention for anticancer drug development since they have aberrantly expressed in distinct cancer types.
References
1.Xinning Zhang,et al. J Cancer Prev. 2018 Sep; 23(3): 109–116.