Cytokinesis

Polo-like kinase 1 regulates Nlp, a centrosome protein involved in microtubule nucleation. Casenghi, M. et al. Dev Cell. 5, 113–125 (2003)

A role for Plk1 phosphorylation of NudC in cytokinesis. Zhou, T. et al. Dev Cell. 5, 127–138 (2003)

Both groups identified new substrates for Polo-like kinase 1 (Plk1), which has important functions in mitosis. Casenghi and colleagues characterized a centrosomal Plk1 substrate, named Nlp (nein-like protein). They found that Nlp associates with γ-tubulin and that it stimulates microtubule nucleation. This process is required for spindle formation and occurs when centrosomes undergo a structural reorganization, known as centrosome maturation, in preparation for mitosis. Phosphorylated Nlp dissociates from centrosomes and no longer binds γ-tubulin, and expression of a Nlp mutant lacking Plk phosphorylation sites causes aberrant mitotic spindles. So, displacement of Nlp from the centrosome might be necessary for centrosome maturation and spindle assembly. Zou et al. identified NudC (nuclear distribution gene C) as a Plk1 substrate in vitro and in vivo. Depletion of NudC by RNA interference induces multiple defects during mitosis, including multinucleation and cell arrest at the midbody stage, which indicates that NudC has a role in cytokinesis.

Ubiquitylation

Requirement for ubiquitin in Tat-mediated transactivation of the HIV-1 promoter. Brès, V. et al. Nature Cell Biol. 5, 754–761 (2003)

Ubiquitylation has emerged as a means to regulate transcription, so Brès et al. investigated whether Tat, the HIV-1 transactivator, is ubiquitylated and what effect this might have. They found that the E3 RING-finger protein Hdm2 ubiquitylates Tat on lysine 71 and that, rather than targeting Tat for degradation, ubiquitylation increases Tat transactivation. This process is required for Tat-mediated HIV-1 replication, although the exact mechanisms remain unclear.

Signalling

QSulf1 remodels the 6-O sulfation states of cell surface heparin sulfate proteoglycans to promote Wnt signaling. Ai, X. et al. J. Cell Biol. 162, 341–351 (2003) (DOI:10.1083/jcb.200212083)

The heparin sulphate (HS) chains of HS proteoglycans (HSPGs) bind ligands and affect signalling, but the regulation of sulphation is unclear. Here, the sulphatase QSulf1 is characterized as a 6-O endosulphatase — it removes internal sulphates from disaccharides. QSulf1, either at the cell surface or the Golgi, desulphates HSPGs to promote Wnt signalling. Ai et al. suggest that, in the absence of QSulf1, HSPGs bind Wnt ligands with high affinity, but that QSulf1-mediated desulphation of HSPGs lowers Wnt binding affinity, thereby allowing Wnts to be 'presented' to their receptors.