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<jats:p>Endoplasmic reticulum (ER) degradation of aberrant proteins is mediated by the ubiquitin-proteasome pathway. Here, a membrane-bound component of the ubiquitin system, Cue1p, was identified. It was shown to recruit the soluble ubiquitin-conjugating enzyme Ubc7p to the ER membrane. In the absence of Cue1p, unassembled and thus cytosolically mislocalized Ubc7p was unable to participate in ER degradation or in the turnover of soluble non-ER proteins. Moreover, ubiquitination by Cue1p-assembled Ubc7p and Ubc6p was a prerequisite for retrograde transport of lumenal substrates out of the ER, which suggests that ubiquitination is mechanistically integrated into the ER degradation process.</jats:p>

<jats:p> <jats:italic>Lhx3</jats:italic> and <jats:italic>Lhx4</jats:italic> ( <jats:italic>Gsh4</jats:italic> ), two closely related LIM homeobox genes, determine formation of the pituitary gland in mice. Rathke's pouch is formed in two steps—first as a rudiment and later as a definitive pouch. <jats:italic>Lhx3</jats:italic> and <jats:italic>Lhx4</jats:italic> have redundant control over formation of the definitive pouch. <jats:italic>Lhx3</jats:italic> controls a subsequent step of pituitary fate commitment. Thereafter, <jats:italic>Lhx3</jats:italic> and <jats:italic>Lhx4</jats:italic> together regulate proliferation and differentiation of pituitary-specific cell lineages. Thus, <jats:italic>Lhx3</jats:italic> and <jats:italic>Lhx4</jats:italic> dictate pituitary organ identity by controlling developmental decisions at multiple stages of organogenesis. </jats:p>

<jats:p> The <jats:italic>ras</jats:italic> proto-oncogene is frequently mutated in human tumors and functions to chronically stimulate signal transduction cascades resulting in the synthesis or activation of specific transcription factors, including Ets, c-Myc, c-Jun, and nuclear factor kappa B (NF-κB). These Ras-responsive transcription factors are required for transformation, but the mechanisms by which these proteins facilitate oncogenesis have not been fully established. Oncogenic Ras was shown to initiate a p53-independent apoptotic response that was suppressed through the activation of NF-κB. These results provide an explanation for the requirement of NF-κB for Ras-mediated oncogenesis and provide evidence that Ras-transformed cells are susceptible to apoptosis even if they do not express the p53 tumor-suppressor gene product. </jats:p>