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Fig. 2. Speculative cartoon to `integrate isolated clues', and stimulate thought. A few interactions described for A-type lamins in the text are illustrated here, speculatively, in the context of lamin filaments near the nuclear inner membrane (IM) or associated with chromatin. Integral membrane proteins nesprin 1
(Nesprin) and emerin (EM) are embedded at the IM. Many other lamin-binding IM proteins are not depicted. NPC, nuclear pore complex. NS, nucleosome. OM, nuclear outer membrane. (Top left) Emerin, representing all LEM-domain proteins, binds BAF. BAF and MOK bind lamins in vitro and inhibit Crx-dependent gene activation in vivo, implicating both proteins in lamin-dependent gene-regulation events. Not depicted are potential gene-regulatory complexes involving nuclear membrane proteins LAP2b (Nili et al., 2001; Foisner, 2003) or lamin B receptor (Östlund and Worman, 2003). Emerin has many direct binding partners including nesprin-1, lamins, actin (not depicted), BAF and several transcription regulators (not shown) (Bengtsson and Wilson, 2004). The number of distinct oligomeric complexes that include emerin is not known. (Top right) Lamin-binding enzyme 12(S)-lipoxygenase [12(S)-LOX] converts arachidonic acid (AA) to 12(S)-hydroxyeicosatetraenoic acid [12(S)-HETE]. We speculate that this reaction occurs in a signaling complex near the inner membrane, where 12(S)-HETE then activates lamin-bound protein kinase C (PKC), leading to phosphorylation of unknown target proteins. (Bottom center) Pairwise interactions, summarized in the text, suggest that one or multiple oligomeric gene-regulation complexes might be formed by LAP2, A-type lamins, retinoblastoma (Rb), E2F/DP heterodimers (gene-specific activators), chromatin-silencing histone deacetylase complex (HDAC), BAF and additional unidentified chromatin partners for LAP2 (Vlcek et al., 2002).
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