May 9, 2008: 30 (3)
"DNA Damage Signals for p53 Pulses"
[Cover Caption]
Browse Archive
 Previews | Pages |
|---|---|
| DNA Polymerases at the Replication Fork in Eukaryotes Bruce Stillman | 259 |
| Too Much of a Good Thing: The Prl-3 in p53's Oyster Philip W. Hinds | 260 |
| SF2/ASF TORCs Up Translation Martin Bushell, Mark Stoneley, Keith A. Spriggs, and Anne E. Willis | 262 |
| AMPK and Raptor: Matching Cell Growth to Energy Supply D. Grahame Hardie | 263 |
| Articles | Pages |
| Colocalization of Sensors Is Sufficient to Activate the DNA Damage Checkpoint in the Absence of Damage Carla Yaneth Bonilla, Justine Amy Melo, and David Paul Toczyski | 267 |
| Recurrent Initiation: A Mechanism for Triggering p53 Pulses in Response to DNA Damage Eric Batchelor, Caroline S. Mock, Irun Bhan, Alexander Loewer, and Galit Lahav | 277 |
| Cdc20 and Cks Direct the Spindle Checkpoint-Independent Destruction of Cyclin A Rob Wolthuis, Lori Clay-Farrace, Wouter van Zon, Mona Yekezare, Lars Koop, Janneke Ogink, René Medema, and Jonathon Pines | 290 |
| The Metastasis-Associated Gene Prl-3 Is a p53 Target Involved in Cell-Cycle Regulation Shashwati Basak, Suzanne B.R. Jacobs, Adam J. Krieg, Navneeta Pathak, Qi Zeng, Philipp Kaldis, Amato J. Giaccia, and Laura D. Attardi | 303 |
| Structures of DNA Polymerase β with Active-Site Mismatches Suggest a Transient Abasic Site Intermediate during Misincorporation Vinod K. Batra, William A. Beard, David D. Shock, Lars C. Pedersen, and Samuel H. Wilson | 315 |
| Microarray-Based Genetic Screen Defines SAW1, a Gene Required for Rad1/Rad10-Dependent Processing of Recombination Intermediates Fuyang Li, Junchao Dong, Xuewen Pan, Ji-Hyun Oum, Jef D. Boeke, and Sang Eun Lee | 325 |
| Regulation of Estrogen Receptor α by the SET7 Lysine Methyltransferase Krithika Subramanian, Da Jia, Priya Kapoor-Vazirani, Doris R. Powell, Robert E. Collins, Dipali Sharma, Junmin Peng, Xiaodong Cheng, and Paula M. Vertino | 336 |
| Coupling of Ribosomal L1 Stalk and tRNA Dynamics during Translation Elongation Jingyi Fei, Pallav Kosuri, Daniel D. MacDougall, and Ruben L. Gonzalez | 348 |
| Mechanism of Gate Opening in the 20S Proteasome by the Proteasomal ATPases Julius Rabl, David M. Smith, Yadong Yu, Shih-Chung Chang, Alfred L. Goldberg, and Yifan Cheng | 360 |
| To Trigger Apoptosis, Bak Exposes Its BH3 Domain and Homodimerizes via BH3:Groove Interactions Grant Dewson, Tobias Kratina, Huiyan W. Sim, Hamsa Puthalakath, Jerry M. Adams, Peter M. Colman, and Ruth M. Kluck | 369 |
| Resource | Pages |
| Comprehensive Identification of PIP3-Regulated PH Domains from C. elegans to H. sapiens by Model Prediction and Live Imaging Wei Sun Park, Won Do Heo, James H. Whalen, Nancy A. O'Rourke, Heather M. Bryan, Tobias Meyer, and Mary N. Teruel | 381 |
Cover Caption
On the cover: A major challenge of systems biology is to understand how network topology affects protein dynamics in living cells. Time-lapse movies of single cells revealed pulses of the tumor suppressor protein p53 in response to DNA damage, yet it is unclear how p53 pulses arise and what controls their shape and timing. To identify the crucial interactions required for p53 pulses, in this issue Batchelor et al. (277–289) combine quantitative experimental analysis of the p53 network with a predictive computational framework. They show that p53 pulses are driven by pulses in the upstream signaling kinases, ATM and Chk2, and that a negative feedback mediated by the phosphatase Wip1 is essential for maintaining the uniform shape of p53 pulses.
Featured Article
- The Metastasis-Associated Gene Prl-3 Is a p53 Target Involved in Cell-Cycle Regulation
Shashwati Basak, Suzanne B.R. Jacobs, Adam J. Krieg, Navneeta Pathak, Qi Zeng, Philipp Kaldis, Amato J. Giaccia, and Laura D. Attardi
[Summary] [Full Text] [PDF] [Supplemental Data] - The p53 tumor suppressor restricts tumorigenesis through the transcriptional activation of target genes involved in cell-cycle arrest and apoptosis. Here, we identify Prl-3 (phosphatase of regenerating liver-3) as a p53-inducible gene. Whereas previous studies implicated Prl-3 in metastasis because of its overexpression in metastatic human colorectal cancer and its ability to promote invasiveness and motility, we demonstrate here that Prl-3 is an important cell-cycle regulator. Consistent with a role in DNA damage-induced cell-cycle arrest, Prl-3 overexpression induces G1 arrest downstream of p53 by triggering a PI3K-Akt-activated negative feedback loop. Surprisingly, attenuation of Prl-3 expression also elicits an arrest response, suggesting that basal level Prl-3 expression is pivotal for normal cell-cycle progression. Our findings highlight key dose-dependent functions of Prl-3 in both positive and negative regulation of cell-cycle progression and provide insight into Prl-3's role in cancer progression.
