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The RAF–MEK–ERK pathway regulates both myoblast proliferation and differentiation; however, it is unclear how these events are coordinated. Here, we show that human phosphatidylethanolamine-binding protein 4 (PEBP4), a RAF kinase inhibitory protein (RKIP) family protein expressed preferentially in muscle, regulates the activity of the ERK pathway and myoblast differentiation by acting as a scaffold protein. In contrast to RKIP, which disrupts the RAF1–MEK interaction, PEBP4 forms ternary complexes with RAF1 and MEK, and can scaffold this interaction. PEBP4 expression is induced during the differentiation of primary human myoblasts. Consistent with the properties of a scaffold, PEBP4 enhances the RAF1–MEK interaction and the activation of MEK at low expression levels, whereas it inhibits these parameters at higher expression levels. Downregulation of PEBP4 by short hairpin RNA in human myoblasts increases MEK signalling and inhibits differentiation; by contrast, PEBP4 overexpression enhances differentiation. Thus, PEBP4 participates in the control of muscle cell differentiation by modulating the activity of MEK and ERK. [ABSTRACT FROM AUTHOR]

The budding yeast spindle pole body (SPB) not only organizes the astral and nuclear microtubules but is also associated with a number of cell-cycle regulators that control mitotic exit. Here, we describe that the core SPB component Nudlp is a key protein that functions in both processes. The astral microtubule organizing function of Nudlp is mediated by its interaction with the γ-tubulin complex binding protein Spc72p. This function of Nudlp is distinct from its role in cell-cycle control: Nudlp binds the spindle checkpoint control proteins Bfalp and Bub2p to the SPB, and is part of the mitotic exit network (MEN) in which it functions upstream of CDC15 but downstream of LTE1. In conditional lethal nudl-2 cells, the MEN component Temlp, a GTPase, is mislocalized, whereas the kinase Cdcl5p is still associated with the SPB. Thus, in nudl-2 cells the failure of Temlp to interact with Cdcl5p at the SPB probably prevents mitotic exit. [ABSTRACT FROM AUTHOR]

Presents correction to the article related to astral microtubule published in 2000 issue of the "The EMBO Journal."