Terminal Uridyltransferase Enzyme Zcchc11 Promotes Cell Proliferation Independent of Its Uridyltransferase Activity
Year: 2011
Type: article
Abstract: Zcchc11 is a uridyltransferase protein with enzymatic activity directed against diverse RNA species. On the basis of its known uridylation targets, we hypothesized that Zcchc11 might regulate cell proliferation. Confirming this, loss-of-function and complementary gain-of-function experiments consistently revealed that Zcchc11 promotes the transition from G(1) to S phase of the cell cycle. This activity takes place through both Rb-dependent and Rb-independent mechanisms by promoting the expression of multiple G(1)-associated proteins, including cyclins D(1) and A and CDK4. Surprisingly, a Zcchc11 construct with point mutations inactivating the uridyltransferase domain enhanced cell proliferation as effectively as wild-type Zcchc11. Furthermore, truncated mutant constructs revealed that the cell cycle effects of Zcchc11 were driven by the N-terminal region of the protein that lacks the RNA-binding domains and uridyltransferase activity of the full protein. Therefore, the N-terminal portion of Zcchc11, which lacks nucleotidyltransferase capabilities, is biologically active and mediates a previously unrecognized role for Zcchc11 in facilitating cell proliferation.
Source: Journal of Biological Chemistry
Institutions: Boston University, Harvard University
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,430
Awards: G1767306420, G4685384675, MicroRNA uridylation by Zcchc11 regulates pulmonary inflammation, NF-kB and Innate Immunity in the Lungs, Cytokine-stimulated systemic defenses during pneumococcal pneumonia, Interdisciplinary Training in Genetics and Complex Disease(RMI), Biology of the Lung: A Multidisciplinary Program
OpenAlex ID: W1992338959