Cyclin D1 determines mitochondrial function in vivo.
نویسندگان
چکیده
The cyclin D1 gene encodes a regulatory subunit of the holoenzyme that phosphorylates and inactivates the pRb tumor suppressor to promote nuclear DNA synthesis. cyclin D1 is overexpressed in human breast cancers and is sufficient for the development of murine mammary tumors. Herein, cyclin D1 is shown to perform a novel function, inhibiting mitochondrial function and size. Mitochondrial activity was enhanced by genetic deletion or antisense or small interfering RNA to cyclin D1. Global gene expression profiling and functional analysis of mammary epithelial cell-targeted cyclin D1 antisense transgenics demonstrated that cyclin D1 inhibits mitochondrial activity and aerobic glycolysis in vivo. Reciprocal regulation of these genes was observed in cyclin D1-induced mammary tumors. Cyclin D1 thus integrates nuclear DNA synthesis and mitochondrial function.
منابع مشابه
Cyclin D1 determines estrogen signaling in the mammary gland in vivo.
The CCND1 gene, which is frequently overexpressed in cancers, encodes the regulatory subunit of a holoenzyme that phosphorylates the retinoblastoma protein. Although it is known that cyclin D1 regulates estrogen receptor (ER)α transactivation using heterologous reporter systems, the in vivo biological significance of cyclin D1 to estrogen-dependent signaling, and the molecular mechanisms by whi...
متن کاملCyclin D1 repression of nuclear respiratory factor 1 integrates nuclear DNA synthesis and mitochondrial function.
Cyclin D1 promotes nuclear DNA synthesis through phosphorylation and inactivation of the pRb tumor suppressor. Herein, cyclin D1 deficiency increased mitochondrial size and activity that was rescued by cyclin D1 in a Cdk-dependent manner. Nuclear respiratory factor 1 (NRF-1), which induces nuclear-encoded mitochondrial genes, was repressed in expression and activity by cyclin D1. Cyclin D1-depe...
متن کاملCyclin D1 inhibits mitochondrial activity in B cells.
Cyclin D1 is a cell cycle regulatory protein that acts at the G1-S transition, following its binding to and activation by the cyclin-dependent kinases 4 or 6. Cyclin D1 is absent from the entire B-cell lineage but is present in a large percentage of 2 types of malignant B-cell hemopathy--mantle cell lymphoma and multiple myeloma--suggesting a major role of this protein in the malignancy process...
متن کاملMolecular and Cellular Pathobiology Cyclin D1 Inhibits Mitochondrial Activity in B Cells
Cyclin D1 is a cell cycle regulatory protein that acts at the G1-S transition, following its binding to and activation by the cyclin-dependent kinases 4 or 6. Cyclin D1 is absent from the entire B-cell lineage but is present in a large percentage of 2 types of malignant B-cell hemopathy—mantle cell lymphoma and multiple myeloma— suggesting a major role of this protein in the malignancy process....
متن کاملP-96: Appositional Expressions of Cyclin D1 and E2F1 Gene Machineries in Mycooestrogen Zeralenone-Induced Apoptosis in Testicular Tissue of Rats
Background: Zearalenone (ZEA) is known as a nonsteroidal oestrogenic mycotoxin produced by different species of Fusarium fungi. ZEA is known for its competitive effects with the natural 17-β estradiol to bind with the specific binding sites of the estrogen receptors (Ers). On the other hand, the cyclin family (especially cyclin D1) and E2F1 genes are the checkpoint genes involved in cell cycle....
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:
- Molecular and cellular biology
دوره 26 14 شماره
صفحات -
تاریخ انتشار 2006