(优选)第二十章癌基因和抑癌基因
合集下载
相关主题
- 1、下载文档前请自行甄别文档内容的完整性，平台不提供额外的编辑、内容补充、找答案等附加服务。
- 2、"仅部分预览"的文档,不可在线预览部分如存在完整性等问题,可反馈申请退款(可完整预览的文档不适用该条件!)。
- 3、如文档侵犯您的权益，请联系客服反馈,我们会尽快为您处理(人工客服工作时间：9:00-18:30)。
• Note: not all oncogenes caused by viruses. • 100’s of oncogenes now known. • Human T-cell leukemia virus (HTLV) is a human RV; codes a
TF.
Retroviral life cycle
Rous Sarcomawenku.baidu.comVirus (RSV)
• Discovered by Harold Varmus and Bishop, 1975-76 (Nobel Prize, 1989).
• A transforming retrovirus: a cancer-causing single-stranded RNA virus that uses reverse transcriptase enzyme to make ssDNA, then ds DNA, which integrates into host DNA.
一、癌基因的基本概念
癌基因（oncogene）是指存在于正常细胞内， 与细胞生长发育调控有关的一组结构基因。
癌基因发生结构异常或表达异常时，可以引起 细胞癌变。
癌基因可按其来源不同而分为病毒癌基因（vonc）和细胞癌基因（c-onc）。
History of oncogene
• Oncogenes were first discovered in certain retroviruses and were later identified as cancer-causing agents in many animals
Oncogenes Stimulate Proliferation Inhibit Differentiation Inhibit Apoptosis
Tumor Suppressor Genes Inhibit Proliferation Promote Differentiation Stimulate Apoptosis
chickens caused new tumors.
Rous Peyton ： The 1966 Nobel Prize in Physiology or Medicine
长末端 重复序列
正常的病毒基因
癌基因
LTR gag
pol
env src LTR
调节和 产生病毒 产生逆转录 产生病毒 产生酪氨酸 启动转录 核心蛋白 酶和整合酶 外膜蛋白 蛋白激酶
• Two different types of mutations contribute to cancer formation: activating mutations in proto-oncogene and inactivating mutations in tumor suppressor genes.
• First link between viruses and cancer
proposed by Francis Peyton Rous in 1910
(Nobel Prize, 1966): cell-free extracts from
chicken tumors injected into healthy
Figure 6 Retroviral life cycle
Retroviruses have two identical copies of a plus single-stranded RNA genome and an outer envelope containing protruding viral glycoproteins. After envelope glycoproteins on a virion interact with a specific host-cell membraneprotein or group of proteins, the retroviral envelope fuses directly with the plasma membrane without first undergoing endocytosis (step 1). Following fusion, the nucleocapsid enters the cytoplasm of the cell; then deoxynucleoside triphosphates from the cytosol enter the nucleocapsid, where viral reverse transcriptase and other proteins copy the ssRNA genome of the virus into a dsDNA copy (step 2). The viral DNA copy is transported into the nucleus (only one host-cell chromosome is depicted) and integrated into one of many possible sites in the host-cell chromosomal DNA (step 3). The integrated viral DNA, referred to as a provirus, is transcribed by the host-cell RNA polymerase, generating mRNAs (light red) and genomic RNA molecules (dark red). The host-cell machinery translates the viral mRNAs into glycoproteins and nucleocapsid proteins (step 4). The latter assemble with genomic RNA to form progeny nucleocapsids, which interact with the membrane-bound viral glycoproteins,. Eventually the host-cell membrane buds out and progeny virions are pinched off (step 5).
Normal
transformed
肿瘤是机体在各种致瘤因素的作用下，局部组织的细胞在基因水平上 失掉了对其生长的正常调控，导致异常增生而形成的新生物。
正常细致胞瘤→因素→ → 基因改变 → 肿瘤细胞
Development of Cancer
• Defective cell cycles checkpoints mechanisms allows errors in the cell duplication process to persist into the next generation and can lead to and regulated proliferation and the development of cancer.
TF.
Retroviral life cycle
Rous Sarcomawenku.baidu.comVirus (RSV)
• Discovered by Harold Varmus and Bishop, 1975-76 (Nobel Prize, 1989).
• A transforming retrovirus: a cancer-causing single-stranded RNA virus that uses reverse transcriptase enzyme to make ssDNA, then ds DNA, which integrates into host DNA.
一、癌基因的基本概念
癌基因（oncogene）是指存在于正常细胞内， 与细胞生长发育调控有关的一组结构基因。
癌基因发生结构异常或表达异常时，可以引起 细胞癌变。
癌基因可按其来源不同而分为病毒癌基因（vonc）和细胞癌基因（c-onc）。
History of oncogene
• Oncogenes were first discovered in certain retroviruses and were later identified as cancer-causing agents in many animals
Oncogenes Stimulate Proliferation Inhibit Differentiation Inhibit Apoptosis
Tumor Suppressor Genes Inhibit Proliferation Promote Differentiation Stimulate Apoptosis
chickens caused new tumors.
Rous Peyton ： The 1966 Nobel Prize in Physiology or Medicine
长末端 重复序列
正常的病毒基因
癌基因
LTR gag
pol
env src LTR
调节和 产生病毒 产生逆转录 产生病毒 产生酪氨酸 启动转录 核心蛋白 酶和整合酶 外膜蛋白 蛋白激酶
• Two different types of mutations contribute to cancer formation: activating mutations in proto-oncogene and inactivating mutations in tumor suppressor genes.
• First link between viruses and cancer
proposed by Francis Peyton Rous in 1910
(Nobel Prize, 1966): cell-free extracts from
chicken tumors injected into healthy
Figure 6 Retroviral life cycle
Retroviruses have two identical copies of a plus single-stranded RNA genome and an outer envelope containing protruding viral glycoproteins. After envelope glycoproteins on a virion interact with a specific host-cell membraneprotein or group of proteins, the retroviral envelope fuses directly with the plasma membrane without first undergoing endocytosis (step 1). Following fusion, the nucleocapsid enters the cytoplasm of the cell; then deoxynucleoside triphosphates from the cytosol enter the nucleocapsid, where viral reverse transcriptase and other proteins copy the ssRNA genome of the virus into a dsDNA copy (step 2). The viral DNA copy is transported into the nucleus (only one host-cell chromosome is depicted) and integrated into one of many possible sites in the host-cell chromosomal DNA (step 3). The integrated viral DNA, referred to as a provirus, is transcribed by the host-cell RNA polymerase, generating mRNAs (light red) and genomic RNA molecules (dark red). The host-cell machinery translates the viral mRNAs into glycoproteins and nucleocapsid proteins (step 4). The latter assemble with genomic RNA to form progeny nucleocapsids, which interact with the membrane-bound viral glycoproteins,. Eventually the host-cell membrane buds out and progeny virions are pinched off (step 5).
Normal
transformed
肿瘤是机体在各种致瘤因素的作用下，局部组织的细胞在基因水平上 失掉了对其生长的正常调控，导致异常增生而形成的新生物。
正常细致胞瘤→因素→ → 基因改变 → 肿瘤细胞
Development of Cancer
• Defective cell cycles checkpoints mechanisms allows errors in the cell duplication process to persist into the next generation and can lead to and regulated proliferation and the development of cancer.