Mitotic Golgi fragmentation is a two-step process in which the pericentriolar Golgi stacks are converted into bulbs and then either undergo further vesicular spreading or fuse with the ER (Colanzi et al

Mitotic Golgi fragmentation is a two-step process in which the pericentriolar Golgi stacks are converted into bulbs and then either undergo further vesicular spreading or fuse with the ER (Colanzi et al., 2003). the specificity of the Ras-MEK cascade by activating ERK1/2-impartial processes. Introduction Extracellular signal-regulated kinases (ERKs) are members of the MAPK family of signaling proteins, which play a crucial role in the intracellular transmission of extracellular signals (Seger and Krebs, 1995; Yoon and Seger, 2006). Induction of this signaling cascade leads to phosphorylation of several target proteins that eventually regulate proliferation and other cellular processes (Yoon and Seger, 2006). The ERK-induced proliferation is usually regulated by a multistep mechanism that involves several cell-cycle Lerociclib (G1T38) stages (Zhang and Liu, 2002), including the regulation of G0, G1, S, and M (Tamemoto et al., 1992; Lavoie et al., 1996; Wright et al., 1999; Zhang and Liu, 2002; Edmunds and Mahadevan, 2004). Thus, aside from its role in the acute transmission of extracellular signals, the ERK cascade plays a role in the regulation of other cellular processes, which are mediated via a large set of effectors (Yoon and Seger, 2006). One role of the ERK cascade is the regulation of G2/M and mitosis progression. Indeed, all components of the cascade were shown to undergo activation during the late G2 and M phases of the cell cycle (Tamemoto et al., 1992; Edelmann et al., 1996; Shapiro et al., 1998). In addition, inhibition of MEKs’ activities by dominant-negative constructs or with pharmacological inhibitors delayed the progression of cells through the same stages (Wright et al., 1999; Roberts et al., 2002). Several molecular mechanisms have been implicated in the regulation of G2/M by the Lerociclib (G1T38) ERK cascade, including the phosphorylation of centromere protein E (Zecevic et al., 1998), SWICSNF (Sif et al., 1998), and polo-like kinase 3 (Plk3) (Xie et al., 2004), as well as the indirect activation of Plk1, Cdc2 (Liu et al., 2004), and Myt1 (Palmer et al., 1998). However, one of the best studied mechanisms by which the cascade can influence mitosis Lerociclib (G1T38) is the regulation of Golgi fragmentation, which is the focus of this study. During mitosis, a mammalian cell needs to split its Golgi apparatus between two daughter cells. The mechanism that allows the proper division to occur is a massive fragmentation of the Golgi into thousands of vesicles that are later shared by the splitting cells (Shorter and Warren, Nr4a3 2002; Colanzi et al., 2003). This process occurs during the prophase/anaphase stages of mitosis, and is essential for the proper progression of cell division (Sutterlin et al., 2002). One of the kinases that participates in the regulation of this process is usually MEK1 (Acharya et al., 1998), which normally acts as an activator of ERK1 and ERK2 (ERK1/2; Yoon and Seger, 2006). Interestingly, these ERKs were not found to be associated with the fragmented Golgi. In addition, it was later shown that MEK action in the Golgi can proceed even in the absence of their NH2-terminal D domain name, which is essential for their activity toward ERK1/2 (Chuderland and Seger, 2005), indicating the presence of a different MEK substrate in the Golgi (Colanzi et al., 2000). In recent years, several MEK1-induced, ERK1/2-impartial proteins were proposed to play a role in mitotic Golgi fragmentation, including an ERK-like protein.