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Mitotic Regulation of Apoptosis in Leukemia

白血病细胞凋亡的有丝分裂调节

基本信息

批准号：
7758840
负责人：
DEBANANDA PATI
金额：
$ 20.68万
依托单位：
BAYLOR COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-02-01 至 2012-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7758840
关键词：
Affinity Chromatography Amino Acids Anaphase Apoptosis Apoptotic B-Lymphocytes Biochemical Biological Assay C-terminal CSPG6 gene Cancer Biology Caspase Cell Cycle Cell Death Cell Line Cell Nucleus Cell Proliferation Cell Therapy Cell physiology Cell-Free System Chromosome Segregation Cleaved cell Complex Cytoplasm DNA biosynthesis Data Death Domain Death Receptor 5 Development Disease Resistance Ensure Enzyme Activation Enzymes Event Family Gel Chromatography Gene Expression Hematologic Neoplasms Hematopoietic Hematopoietic Neoplasms Human Immunoprecipitation In Vitro Induction of Apoptosis Ion Exchange Joints Laboratories Lead Leukemic Cell Link Malignant - descriptor Malignant Neoplasms Mass Spectrum Analysis Mediating Metaphase Mitochondria Mitosis Mitotic Mitotic Cell Cycle Nuclear Nuclear Protein Nuclear Proteins Pathway interactions Peptide Hydrolases Phosphoric Monoester Hydrolases Phosphotransferases Play Process Proteins Regulation Research Research Personnel Resistance Role Series Signal Transduction Sister Chromatid Site Staging Stimulus System T-Cell Leukemia Techniques Testing Tetanus Helper Peptide Tumor Necrosis Factor Receptor Two-Hybrid System Techniques Work Yeasts base cancer cell carcinogenesis cell growth chemotherapy cohesin cohesion design genetic regulatory protein in vivo leukemia leukemia/lymphoma link protein novel protein aminoacid sequence protein protein interaction receptor repaired response segregation separase therapy resistant treatment strategy yeast two hybrid system

项目摘要

Much of the current effort in cancer biology is concentrated on studying either the cell growth and proliferation or the programmed cell death (apoptosis) pathways individually, and little is known about the coregulation of these two vital processes. Understanding processes and controls common to both cell proliferation and apoptosis would provide a new paradigm for identifying novel targets in the treatment of hematologic malignancies and other cancers. We propose that the processes of mitotic segregation and apoptosis are mechanistically linked and that proteins important for sister chromatid cohesion play a role in regulating normal apoptotic processes. Deregulation of this joint process can lead to formation and progression of hematologic cancers and development of therapy-resistant leukemia and lymphoma. Cohesin Rad21, a mitotic regulatory protein may play an important role in the interface between cell proliferation and apoptosis. Rad21 functions in chromosome segregation and DMAdamage repair during cell proliferation but promotes cell death once apoptosis is induced. Our lab is one of two laboratories that have recently identified a novel role for Rad21 in apoptosis. To test the central hypothesis that mitotic segregation and apoptosis are linked processes, we will focus on specific roles of the cohesin protein Rad21 in apoptosis. Our aims are (a) to identify the nuclear protease that cleaves Rad21 in the nucleus at the early stage of apoptosis induction and to elucidate its role in Rad21 -mediated apoptosis, (b) to identify proteins interacting with C-terminal Rad21 in the apoptotic pathway, and (c) to determine the pathways through which C-terminal Rad21 amplifies apoptotic signals and activates effector caspases in leukemia cell lines. The series of studies proposed will provide novel information about how mitotic proteins regulate apoptosis and their role in carcinogenesis. Understanding the details of cohesin cleavage and subsequent steps in the apoptotic cascade in leukemic cells is expected to lead to the identification of novel targets and strategies for the treatment of hematologic cancers. Furthermore, identification of the mechanism through which C- terminal Rad21 promotes programmed cell death will help explain why leukemic cells are able to evade and resist apoptosis and will aid the design of new strategies for treating chemotherapy-resistant leukemia.

目前在癌症生物学上的大部分努力都集中在研究细胞生长和

项目成果

期刊论文数量（12）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Higher-order orchestration of hematopoiesis: is cohesin a new player?

造血的高阶编排：粘蛋白是新玩家吗？

DOI：
10.1016/j.exphem.2012.09.010
发表时间：
2012-12
期刊：
EXPERIMENTAL HEMATOLOGY
影响因子：
2.6
作者：
Panigrahi, Anil K.;Pati, Debananda
通讯作者：
Pati, Debananda

Spatial quantitation of FISH signals in diploid versus aneuploid nuclei.

二倍体与非整倍体细胞核中 FISH 信号的空间定量。

DOI：
10.1002/cyto.a.22426
发表时间：
2014
期刊：
Cytometry. Part A : the journal of the International Society for Analytical Cytology
影响因子：
0
作者：
Shete,Amol;Rao,Pulivarthi;Pati,Debananda;Merchant,Fatima
通讯作者：
Merchant,Fatima

Handcuff for sisters: a new model for sister chromatid cohesion.

DOI：
10.4161/cc.8.3.7586
发表时间：
2009-02-01
期刊：
Cell cycle (Georgetown, Tex.)
影响因子：
0
作者：
Zhang N;Pati D
通讯作者：
Pati D

MMTV-Espl1 transgenic mice develop aneuploid, estrogen receptor alpha (ERα)-positive mammary adenocarcinomas.

DOI：
10.1038/onc.2013.493
发表时间：
2014-11-27
期刊：
Oncogene
影响因子：
8
作者：
通讯作者：

Separase loss of function cooperates with the loss of p53 in the initiation and progression of T- and B-cell lymphoma, leukemia and aneuploidy in mice.

DOI：
10.1371/journal.pone.0022167
发表时间：
2011
期刊：
PloS one
影响因子：
3.7
作者：
Mukherjee M;Ge G;Zhang N;Huang E;Nakamura LV;Minor M;Fofanov V;Rao PH;Herron A;Pati D
通讯作者：
Pati D