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Full-Text Articles in Medicine and Health Sciences
Xpo1 Blockade With Kpt-330 Promotes Apoptosis In Cutaneous T-Cell Lymphoma By Activating The P53-P21 And P27 Pathways, Nitin Chakravarti, Amy Boles, Rachel Burzinski, Paola Sindaco, Colleen Isabelle, Kathleen Mcconnell, Anjali Mishra, Pierluigi Porcu
Xpo1 Blockade With Kpt-330 Promotes Apoptosis In Cutaneous T-Cell Lymphoma By Activating The P53-P21 And P27 Pathways, Nitin Chakravarti, Amy Boles, Rachel Burzinski, Paola Sindaco, Colleen Isabelle, Kathleen Mcconnell, Anjali Mishra, Pierluigi Porcu
Kimmel Cancer Center Faculty Papers
Dysregulated nuclear-cytoplasmic trafficking has been shown to play a role in oncogenesis in several types of solid tumors and hematological malignancies. Exportin 1 (XPO1) is responsible for the nuclear export of several proteins and RNA species, mainly tumor suppressors. KPT-330, a small molecule inhibitor of XPO1, is approved for treating relapsed multiple myeloma and diffuse large B-cell lymphoma. Cutaneous T-cell lymphoma (CTCL) is an extranodal non-Hodgkin lymphoma with an adverse prognosis and limited treatment options in advanced stages. The effect of therapeutically targeting XPO1 with KPT-330 in CTCL has not been established. We report that XPO1 expression is upregulated in …
Distinct P53 Acetylation Cassettes Differentially Influence Gene-Expression Patterns And Cell Fate., Chad D Knights, Jason Catania, Simone Di Giovanni, Selen Muratoglu, Ricardo Perez, Amber Swartzbeck, Andrew A Quong, Xiaojing Zhang, Terry Beerman, Richard Pestell, Maria Laura Avantaggiati
Distinct P53 Acetylation Cassettes Differentially Influence Gene-Expression Patterns And Cell Fate., Chad D Knights, Jason Catania, Simone Di Giovanni, Selen Muratoglu, Ricardo Perez, Amber Swartzbeck, Andrew A Quong, Xiaojing Zhang, Terry Beerman, Richard Pestell, Maria Laura Avantaggiati
Kimmel Cancer Center Faculty Papers
The activity of the p53 gene product is regulated by a plethora of posttranslational modifications. An open question is whether such posttranslational changes act redundantly or dependently upon one another. We show that a functional interference between specific acetylated and phosphorylated residues of p53 influences cell fate. Acetylation of lysine 320 (K320) prevents phosphorylation of crucial serines in the NH(2)-terminal region of p53; only allows activation of genes containing high-affinity p53 binding sites, such as p21/WAF; and promotes cell survival after DNA damage. In contrast, acetylation of K373 leads to hyperphosphorylation of p53 NH(2)-terminal residues and enhances the interaction with …