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To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.cell.2005.03.037 Byline: Delin Chen (1), Ning Kon (1), Muyang Li (1), Wenzhu Zhang (1), Jun Qin (2), Wei Gu Abstract: Although the importance of the ARF tumor suppressor in p53 regulation is well established, numerous studies indicate that ARF also suppresses cell growth in a p53/Mdm2-independent manner. To understand the mechanism of ARF-mediated tumor suppression, we identified a ubiquitin ligase, ARF-BP1, as a key factor associated with ARF in vivo. ARF-BP1 harbors a signature HECT motif, and its ubiquitin ligase activity is inhibited by ARF. Notably, inactivation of ARF-BP1, but not Mdm2, suppresses the growth of p53 null cells in a manner reminiscent of ARF induction. Surprisingly, in p53 wild-type cells, ARF-BP1 directly binds and ubiquitinates p53, and inactivation of endogenous ARF-BP1 is crucial for ARF-mediated p53 stabilization. Thus, our study modifies the current view of ARF-mediated p53 activation and reveals that ARF-BP1 is a critical mediator of both the p53-independent and p53-dependent tumor suppressor functions of ARF. As such, ARF-BP1 may serve as a potential target for therapeutic intervention in tumors regardless of p53 status. Author Affiliation: (1) Institute for Cancer Genetics, Department of Pathology, College of Physicians and Surgeons, Columbia University, 1150 St. Nicholas Avenue, New York, New York 10032 (2) Departments of Biochemistry and Cell Biology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030 Article History: Received 13 September 2004; Revised 24 February 2005; Accepted 30 March 2005 Article Note: (miscellaneous) Published: June 30, 2005

Results demonstrate that mammalian Sir2alpha interacts with p53 inhibiting deacetylation of p53 as well as enhancing acetylation of p53 in vivo. Data also suggest that Sir2alpha represses p53-dependent apoptosis during DNA damage and oxidative stress.

The deacetylation and repression of the activity of forkhead transcription factor - Foxo3a and other mammalian forkhead factors by the mammalian SIR2 ortholog SIRT1 is reported. The speculation over the down regulation of the two classes of damage - responsive mammalian factors, favoring longer life - span under specific environmental conditions is presented.

Examines the direct interactions between hypoxia-inducible factor 1 alpha (HIF-1 alpha) and Mdm2 modulate p53 function. Response to various types of stress; Protection by HIF-1 alpha of p53 degradation mediated by Mdm2; Implications regarding the molecular mechanism by which p53 is activated by HIF-1 alpha in response to hypoxia; Cell culture and transfection.

• Human metapneumovirus (HMPV) is an important respiratory pathogen that causes acute respiratory tract infection in children ≤5 years old. • The prevalence peak of HMPV in southern China appeared between March and May. • Respiratory syncytial virus is the most common respiratory virus coinfected with HMPV in children. • The predominant subtype of HMPV in this area is B1, followed by A2c subtype. • Long sunshine duration might decrease the HMPV prevalence. This study aimed to determine the epidemiological and genetic features of human metapneumovirus (HMPV) infection in children in southern China, and the effect of meteorological factors on infection. 14,817 children (≤14 years) with acute respiratory tract infections from 2010 to 2019 were examined for HMPV and other respiratory viruses by real-time quantitative polymerase chain reaction. Full-length F gene of 54 positive samples were sequenced and subjected to phylogenetic analysis. The correlation between the HMPV-positive rate and meteorological factors was analyzed by linear regression analysis. HMPV was detected in 524 (3.5%) children, who were mostly younger than 1 year. The seasonal peak of HMPV prevalence mainly occurred in spring. Respiratory syncytial virus was the most common virus coinfected with HMPV (5.3%). Phylogenetic analysis revealed that the sequenced HMPV strains belonged to four sublineages, including A2b (1.9%), A2c (31.5%), B1 (50.0%), and B2 (16.7%). After adjusting for all meteorological factors, sunshine duration was inversely correlated with the HMPV-positive rate. HMPV is an important respiratory pathogen that causes acute respiratory tract infections in children in southern China, particularly in children ≤5 years old. The prevalence peak of HMPV in this area appeared in spring, and the predominant subtype was B1. Meteorological factors, especially long sunshine duration, might decrease the HMPV prevalence. [ABSTRACT FROM AUTHOR]