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Full-Text Articles in Medicine and Health Sciences
Bromodomain And Histone Acetyltransferase Domain Specificities Control Mixed Lineage Leukemia Phenotype, Donna Santillan, C. Theisler, A. Ryan, R. Popovic, T. Stuart, M. Zhou, S. Alkan, N. Zeleznik-Le
Bromodomain And Histone Acetyltransferase Domain Specificities Control Mixed Lineage Leukemia Phenotype, Donna Santillan, C. Theisler, A. Ryan, R. Popovic, T. Stuart, M. Zhou, S. Alkan, N. Zeleznik-Le
Donna A. Santillan
A critical unanswered question about mixed lineage leukemia (MLL) is how specific MLL fusion partners control leukemia phenotype. The MLL-cyclic AMP-responsive element binding protein-binding protein (CBP) fusion requires both the CBP bromodomain and histone acetyltransferase (HAT) domain for transformation and causes acute myelogenous leukemia (AML), often preceded by a myelodysplastic phase. We did domain-swapping experiments to define whether unique specificities of these CBP domains drive this specific MLL phenotype. Within MLL-CBP, we replaced the CBP bromodomain or HAT domain with P300/CBP-associated factor (P/CAF) or TAF(II)250 bromodomains or the P/CAF or GCN5 HAT domains. HAT, but not bromodomain, substitutions conferred enhanced …
Molecular Analysis Of The Neuropeptide Y1 Receptor Gene In Human Idiopathic Gonadotropin-Dependent Precocious Puberty And Isolated Hypogonadotropic Hypogonadism, K. C. Freitas, Ginny Ryan, V. N. Brito, Y. X. Tao, E. M. Costa, B. B. Mendonca, D. Segaloff, A. C. Latronico
Molecular Analysis Of The Neuropeptide Y1 Receptor Gene In Human Idiopathic Gonadotropin-Dependent Precocious Puberty And Isolated Hypogonadotropic Hypogonadism, K. C. Freitas, Ginny Ryan, V. N. Brito, Y. X. Tao, E. M. Costa, B. B. Mendonca, D. Segaloff, A. C. Latronico
Ginny L. Ryan
OBJECTIVE: To investigate the role of mutations or polymorphisms in the NPY-Y1R gene in human idiopathic central pubertal disorders. DESIGN: Molecular studies. SETTING: University hospital. PATIENT(S): Thirty-three patients with gonadotropin-dependent precocious puberty, 22 with hypogonadotropic hypogonadism, and 50 controls. INTERVENTION(S): Genomic DNA extraction, NPY-Y1R gene sequence analysis, cell-surface expression, and functional activity of an identified receptor variant. MAIN OUTCOME MEASURE(S): Results of sequencing, cell-surface receptor expression, and receptor function. RESULT(S): A heterozygous substitution of lysine (K) by threonine (T) at position 374 in the carboxyl terminal region of NPY-Y1R was identified in a girl with familial GDPP. Her mother, who …
Cytoplasmic Metadherin (Mtdh) Provides Survival Advantage Under Conditions Of Stress By Acting As Rna-Binding Protein, Xiangbing Meng, Danlin Zhu, Shujie Yang, Xinjun Wang, Zhi Xiong, Yuping Zhang, Pavla Brachova, Kimberly Leslie
Cytoplasmic Metadherin (Mtdh) Provides Survival Advantage Under Conditions Of Stress By Acting As Rna-Binding Protein, Xiangbing Meng, Danlin Zhu, Shujie Yang, Xinjun Wang, Zhi Xiong, Yuping Zhang, Pavla Brachova, Kimberly Leslie
Xiangbing Meng
Overexpression of metadherin (MTDH) has been documented in many solid tumors and is implicated in metastasis and chemoresistance. MTDH has been detected at the plasma membrane as well as in the cytoplasm and nucleus, and the function of MTDH in these locales remains under investigation. In the nucleus, MTDH acts as a transcription co-factor to induce expression of chemoresistance-associated genes. However, MTDH is predominantly cytoplasmic in prostate tumors, and this localization correlates with poor prognosis. Herein, we used endometrial cancer cells as a model system to define a new role for MTDH in the cytoplasm. First, MTDH was primarily localized …
Cytoplasmic Metadherin (Mtdh) Provides Survival Advantage Under Conditions Of Stress By Acting As Rna-Binding Protein, Xiangbing Meng, Danlin Zhu, Shujie Yang, Xinjun Wang, Zhi Xiong, Yuping Zhang, Pavla Brachova, Kimberly Leslie
Cytoplasmic Metadherin (Mtdh) Provides Survival Advantage Under Conditions Of Stress By Acting As Rna-Binding Protein, Xiangbing Meng, Danlin Zhu, Shujie Yang, Xinjun Wang, Zhi Xiong, Yuping Zhang, Pavla Brachova, Kimberly Leslie
Kimberly K. Leslie
Overexpression of metadherin (MTDH) has been documented in many solid tumors and is implicated in metastasis and chemoresistance. MTDH has been detected at the plasma membrane as well as in the cytoplasm and nucleus, and the function of MTDH in these locales remains under investigation. In the nucleus, MTDH acts as a transcription co-factor to induce expression of chemoresistance-associated genes. However, MTDH is predominantly cytoplasmic in prostate tumors, and this localization correlates with poor prognosis. Herein, we used endometrial cancer cells as a model system to define a new role for MTDH in the cytoplasm. First, MTDH was primarily localized …