INTERACTION BETWEEN RB PROTEIN AND HMG1/2

RB 蛋白和 HMG1/2 之间的相互作用

基本信息

批准号：
6070454
负责人：
ANTON CHESTUKHIN
金额：
$ 4.09万
依托单位：
DANA-FARBER CANCER INST
依托单位国家：
美国
项目类别：
财政年份：
2000
资助国家：
美国
起止时间：
2000-09-01 至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/6070454
关键词：
Baculoviridae Insecta SDS polyacrylamide gel electrophoresis affinity chromatography autoradiography chimeric proteins gene induction /repression genetic promoter element glutathione transferase immunoprecipitation intermolecular interaction luciferin monooxygenase nonhistone nucleoprotein plasmids reporter genes retinoblastoma protein transcription factor transfection /expression vector

项目摘要

The of retinoblastoma susceptibility gene product (pRb) is a potent tumor supressor that is frequently mutated in numerous malignancies including leukemias. pRb and related proteins, p107 and p130 binds to and inactivates different members of the E2F family of transcription factors. In addition to E2F pRb can interact with other factors that modulate transcriptional activity of the pRb-E2F complexes such as: HBP1 (HMG-box- containing transcriptional repressor), hBRGl and hBRM (mammalian homologues of SNF2/SWI2 yeast transcription activator), and histone deacetylase (the enzyme involved in chromatin structure rearrangement) have all been reported to interact with pRb and to modulate its transcriptional activity. Binding of each of these modulators to pRb occur in an LXCXE motif-dependent manner. The LXCXE motif was originally found in certain viral oncoproteins (SV40 T antigen, HPV-16 E7, adenoviral E1A) that also are known to bind to pRb. Preliminary results from our laboratory raised a possibility that pRb may also interact with the HMG1/2 class of proteins. The HMG proteins are nuclear, non-histone structural elements of chromatin that contain an LXCXE motif. We propose to investigate whether the HMG class of proteins contributes to the pRb-dependent regulation of transcription. To address this question we will study specific association of HMG2 and pRB in vitro and in vivo model systems. To investigate the functional significance of HMG2/pRb interaction we will examine effect of HMG on pRb ability to repress transcription in model assays.

视网膜母细胞瘤易感基因产物（PRB）是一种有效的肿瘤supressor，在包括白血病在内的许多恶性肿瘤中经常被突变。 PRB及相关蛋白P107和P130与E2F转录因子家族的不同成员结合并灭活。 In addition to E2F pRb can interact with other factors that modulate transcriptional activity of the pRb-E2F complexes such as: HBP1 (HMG-box- containing transcriptional repressor), hBRGl and hBRM (mammalian homologues of SNF2/SWI2 yeast transcription activator), and histone deacetylase (the enzyme involved in chromatin structure rearrangement) have all been reported to interact使用PRB并调节其转录活性。这些调节剂中的每一个与PRB的结合以LXCXE基序依赖性方式发生。 LXCXE基序最初是在某些病毒癌蛋白（SV40 T抗原，HPV-16 E7，腺病毒E1A）中发现的，该病毒蛋白蛋白也已知与PRB结合。我们实验室的初步结果提出了PRB也可能与HMG1/2类蛋白质相互作用的可能性。 HMG蛋白是含有LXCXE基序的核，非内酮结构元素。我们建议研究HMG类蛋白的类别是否有助于依赖PRB的转录调节。为了解决这个问题，我们将在体外和体内模型系统中研究HMG2和PRB的特定关联。为了研究HMG2/PRB相互作用的功能意义，我们将研究HMG对PRB在模型测定中抑制转录能力的影响。