Swapping nucleotides, tuning Hsp70

Molecular chaperones such as heat shock protein 70 (Hsp70) are crucial for protein folding. Crystal structures of Hsp70 in a complex with the nucleotide exchange factor (NEF) Hsp110 reported in this issue of Cell (Polier et al., 2008) and in Molecular Cell (Schuermann et al., 2008) provide new insights into how NEF action specifies Hsp70 cellular function.     

Mitochondrial dynamics and apoptosis: a painful separation

Reporting in Molecular Cell, Sheridan et al. (2008) and Breckenridge et al. (2008) show that mitochondrial fragmentation is not required to induce cell death. Meanwhile, Yamaguchi et al. show that proapoptotic Bcl-2 family members promote cytochrome c mobilization through Opa1-mediated cristae remodeling. Therefore, the connection between mitochondrial structure and apoptosis is more complex than previously imagined.     

Death by splicing: tumor suppressor RBM5 freezes splice-site pairing

In a recent issue of Molecular Cell, Bonnal et al. (2008) demonstrate that the tumor suppressor gene RBM5 regulates alternative splicing of Fas pre-mRNA by interfering with splice-site pairing.     

GU-rich RNA: expanding CUGBP1 function, broadening mRNA turnover

In this issue of Molecular Cell, Vlasova et al. (2008) identify the GU-rich element (GRE) as a novel, widespread, degradation-promoting sequence through which the RNA-binding protein CUGBP1 elicits mRNA decay.     

A ubiquitin-like protein unleashes ubiquitin ligases

Modification of cullin-RING ubiquitin ligases by the ubiquitin-like molecule Nedd8 promotes substrate ubiquitination. A crystal structure of a cullin modified by Nedd8 recently reported in Cell (Duda et al., 2008) and a biochemical study in Molecular Cell (Saha and Deshaies, 2008) reveal the dramatic impact on the ligase machinery by conjugation of ubiquitin or ubiquitin-like proteins.     

From DNA end chemistry to cell-cycle response: the importance of structure, even when it's broken

In this issue of Molecular Cell, Barlow et al. (2008) show that not all DNA double-strand breaks are processed equally and that the chemical nature of DNA ends guides different paths to DNA repair.     

A very private TGF-beta receptor embrace

In this issue of Molecular Cell, Groppe et al. (2008) describe the crystal structure of a six-element TGF-beta:receptor complex, addressing long-standing questions about the restrictive nature of this vital receptor interaction.     

SF2/ASF TORCs up translation

In a recent issue of Molecular Cell, Michlewski et al. (2008) show that SF2/ASF, a splicing factor, stimulates translation initiation by directly recruiting the mammalian target of rapamycin (mTOR) to a subset of mRNAs.     

mTOR and Akt signaling in cancer: SGK cycles in

In a recent issue of Molecular Cell, Hong et al. (2008) describe an alternative mechanism by which mTOR promotes cell-cycle progression; it phosphorylates and activates SGK, which in turn phosphorylates the cell-cycle inhibitor p27, promoting its cytoplasmic retention.     

Gene regulation: hacking the network on a sugar high

In a recent issue of Molecular Cell, Lee et al. (2008) demonstrate that the forkhead-associated (FHA) domain of Dun1, a Chk2-related kinase involved in DNA damage signaling, selectively binds a diphosphorylated motif found in its paralog and upstream regulator Rad53.     

Increased mTORC1 signaling UPRegulates stress

In this issue of Molecular Cell, Ozcan et al. (2008) show that the loss of the tuberous sclerosis tumor suppressor complex induces endoplasmic reticulum stress, leading to attenuation of insulin receptor signaling activity via the unfolded protein response.     

Hit and run: transient deubiquitylase activity in a chromatin-remodeling complex

In this issue of Molecular Cell, Conaway and colleagues (Yao et al., 2008) provide a glimpse into an interesting mechanism to control a deubiquitylating enzyme via interaction of two complexes-the 19S proteasome regulatory particle and an ATP-dependent nucleosome remodeling complex.     

ATM breaks into heterochromatin

Heterochromatin is refractory to DNA transactions, including repair. In a recent issue of Molecular Cell, Goodarzi et al. (2008) reveal how the central transducing kinase of the DNA damage response relieves this natural barrier by increasing heterochromatic DNA accessibility.     

Tbf1 or not Tbf1?

In this issue of Molecular Cell, Hogues et al. (2008) demonstrate a wholesale shift in the key regulatory protein involved in ribosomal protein (RP) synthesis during the evolution of S. cerevisiae and, en passant, raise interesting questions about the relationship between RP genes and telomeres.     

CHIPping away at base excision repair

In this issue of Molecular Cell, Parsons et al. (2008) report that the E3 ubiquitin ligase CHIP regulates the stability of the base excision repair (BER) proteins XRCC1 and DNA Pol beta, adding a new level of regulation for BER.