Mechanisms of cell transformation induced by polyomavirus.
نویسندگان
چکیده
Polyomavirus is a DNA tumor virus that induces a variety of tumors in mice. Its genome encodes three proteins, namely large T (LT), middle T (MT), and small T (ST) antigens, that have been implicated in cell transformation and tumorigenesis. LT is associated with cell immortalization, whereas MT plays an essential role in cell transformation by binding to and activating several cytoplasmic proteins that participate in growth factor-induced mitogenic signal transduction to the nucleus. The use of different MT mutants has led to the identification of MT-binding proteins as well as analysis of their importance during cell transformation. Studying the molecular mechanisms of cell transformation by MT has contributed to a better understanding of cell cycle regulation and growth control.
منابع مشابه
How does the Merkel polyomavirus lead to a lethal cancer? Many answers, many questions, and a new mouse model
The Merkel cell polyomavirus (MCPyV), discovered in 2008, drives the development of most Merkel cell carcinomas (MCCs) through several canonical mechanisms. A glaring gap in our knowledge remains the basis by which MCPyV, among all 12 human polyomaviruses, is the only one that causes cancer in humans. Moreover, initial attempts by numerous groups have failed to reproduce MCC in mice using oncop...
متن کاملMerkel cell polyomavirus small T antigen controls viral replication and oncoprotein expression by targeting the cellular ubiquitin ligase SCFFbw7.
Merkel cell polyomavirus (MCV) causes an aggressive human skin cancer, Merkel cell carcinoma, through expression of small T (sT) and large T (LT) viral oncoproteins. MCV sT is also required for efficient MCV DNA replication by the multifunctional MCV LT helicase protein. We find that LT is targeted for proteasomal degradation by the cellular SCF(Fbw7) E3 ligase, which can be inhibited by sT thr...
متن کاملMerkel Cell Polyomavirus Small T Antigen Mediates Microtubule Destabilization To Promote Cell Motility and Migration
UNLABELLED Merkel cell carcinoma (MCC) is an aggressive skin cancer of neuroendocrine origin with a high propensity for recurrence and metastasis. Merkel cell polyomavirus (MCPyV) causes the majority of MCC cases due to the expression of the MCPyV small and large tumor antigens (ST and LT, respectively). Although a number of molecular mechanisms have been attributed to MCPyV tumor antigen-media...
متن کاملTransformation and tumorigenic properties of a mutant polyomavirus containing a middle T antigen defective in Shc binding.
Polyomavirus middle T antigen is phosphorylated on several tyrosine residues which act as binding sites for cellular proteins, including phosphatidylinositol 3-kinase, Shc, and phospholipase C-gamma. In this report we describe the transforming properties and tumor-inducing ability of a polyomavirus that contains a single-site mutation in middle T antigen which changes a tyrosine residue at amin...
متن کاملMerkel Cell Polyomavirus Small T Antigen Promotes Pro-Glycolytic Metabolic Perturbations Required for Transformation
Merkel cell polyomavirus (MCPyV) is an etiological agent of Merkel cell carcinoma (MCC), a highly aggressive skin cancer. The MCPyV small tumor antigen (ST) is required for maintenance of MCC and can transform normal cells. To gain insight into cellular perturbations induced by MCPyV ST, we performed transcriptome analysis of normal human fibroblasts with inducible expression of ST. MCPyV ST dy...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas
دوره 32 7 شماره
صفحات -
تاریخ انتشار 1999