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Mol Cell Biol. 2010 February; 30(4): 885.
PMCID: PMC2815563

Articles of Significant Interest Selected from This Issue by the Editors

Functional Antagonism of bZip Transcription Factors Mediates Oscillatory Gene Expression

Pulsatile hormone synthesis and secretion are critical for physiological processes, with disruption of episodic hormone release often associated with clinical disorders. Oscillatory follicle-stimulating hormone (FSH) and luteinizing hormone secretion is under the control of pulsatile gonadotropin-releasing hormone (GnRH), with FSHβ transcription preferentially stimulated at low rather than high GnRH pulse frequencies. Ciccone et al. (p. 1028-1040) have elucidated a mechanism by which these differential effects are orchestrated by two bZip family members, CREB and ICER. High GnRH pulse frequencies preferentially induce the transcriptional repressor ICER, which antagonizes CREB-mediated FSHβ stimulation to attenuate FSHβ expression. Our findings highlight ICER as a major integrative player in the maintenance of biological rhythms.

Processivity of Degradation by the 26S Proteasome: Role of a Proteasome-Associated Ubiquitin Ligase

Polyubiquitination serves as a tag that targets proteins destined for degradation to the 26S proteasome, where they normally are processively hydrolyzed to short peptides. The role of Hul5, a HECT-type ubiquitin ligase associated with the proteasome itself, was until now uncertain. Aviram et al. (p. 985-994) show that for some challenging, hard-to- unfold substrates, which due to their structure are partially processed rather than fully degraded by the proteasome, the ubiquitination activity of Hul5 helps promote complete degradation. This work raises the question of whether ubiquitination, beyond functioning as a tag, could directly promote protein unfolding.

Akt2: a Gatekeeper for Osteogenesis?

Mesenchymal stem cells are essential for repair of bone. Bone morphogenetic proteins (BMPs) promote their commitment toward an osteogenic fate by inducing expression of Dlx5 and Runx2, critical transcription factors that orchestrate osteoblast differentiation. Other growth factors also influence osteogenesis. Mukherjee et al. (p. 1018-1027) use targeted knockdown and gene replacement strategies to show that activation of Akt2 by insulinlike growth factor signaling is necessary for BMP-2-stimulated expression of Runx2 and osteoblast differentiation, while Akt1 is dispensable. Their results highlight potentially unique actions of individual Akts in mesenchymal precursor development that will require new strategies to identify critical signaling mechanisms.

Telomeres: the Importance of Staying Connected

Telomeres solve the end protection problem with shelterin, a multisubunit protein complex that accumulates on telomeric DNA. Mouse shelterin contains two single-stranded DNA binding proteins, POT1a and POT1b, which repress the activation of the ATR kinase at chromosome ends. Both POT1 proteins interact with TPP1, which in turn binds to shelterin subunits associated with the double-stranded telomeric DNA. Kibe et al. (p. 1059-1066) performed studies with mouse cells lacking TPP1 and conclude that the major function of TPP1 is to bring the POT1 proteins to the telomere, thereby facilitating loading of POT1 onto the single-stranded telomeric DNA, where it represses ATR kinase signaling.

Articles from Molecular and Cellular Biology are provided here courtesy of American Society for Microbiology (ASM)