annotation review human Cep57

[ValWood]

human Cep57 https://www.uniprot.org/uniprot/Q86XR8

Centrosomal protein which may be required for microtubule attachment to centrosomes. May act by forming ring-like structures around microtubules. Mediates nuclear translocation and mitogenic activity of the internalized growth factor FGF2, but that of FGF1.1 Publication

these descriptions are conflicting because being involved in centrosome/microtubule attachment doesn't really coincide with nuclear transport.

the protein import into nucleus, translocation seems to come from https://www.uniprot.org/citations/12717444 a TAS annotation, but this papers seems to be about FGF-1 and FGF-2 which are not listed as synonyms for Cep57

(note that Cep57 is also called FGF2-interacting protein. This would not be contradictory with a centrosomal role, but does not necessarily imply a role in nucleocytoplasmic transport.

[deustp01]

A two-part thought here. The first is that some proteins are good at sticking to diverse stuff. Here the authors are claiming that, unlike the case of actin, the stickiness is physiologically relevant and specific. (No clue whether the experiments really show that.) The second is a recollection from 10 years ago that, somewhere in the vicinity of the RAN small GTPase and its associated proteins there really are proteins that both play a role in transport through the nuclear pore in interphase and in mitotic spindle assembly and function during mitosis, so this pair of functions isn't a priori impossible. All our annotations for the protein are of functions involving centrosomes.

[ValWood]

It's not impossible. However there is no evidence. The paper providing the TAS for Cep57 does not mention Cep57, or its synonyms TSP57?

[ValWood]

Oh it's "translokin" in the title! OK so this paper Is about cep57

[ValWood]

HA–FGF-2, which were concentrated in the centrosome area. To determine whether the intracellular transport of exogenous FGF-2 was dependent on microtubules, we carried out experiments with depolymerizing drugs. Cytochalasin B, which targets actin microfilaments (Fig. 4b, compare the actin filament distribution in rows 4 and 5), did not alter the distribution of FGF-2 in the nuclear region. By contrast, treatment with nocodazole, which causes depolymerization of microtubules (Fig. 4b, compare the microtubule organization in rows 2 and 5), prevented the appearance of FGF-2 in the juxtanuclear region (Fig. 4b, row 3). In these cells, punctuated FGF-2 staining was found in the cytoplasm, especially in the vicinity of the plasma membrane. These results indicate that the intracellular trafficking of exogenous 18K FGF-2 may be mediated by microtubules in ABAE cells and that it correlates with the microtubule-associated pattern of Translokin observed by immunocytochemistry (Supplementary Information Fig. S1c). We considered that if nuclear translocation is important for the mitogenic activity of FGF-2, then it might be possible to restore the mitogenic activity of Nb1a2 by fusing an NLS derived from the SV40 T antigen (PKKKRKKV) to its N terminus. We therefore produced and purified recombinant NLS–Nb1a2 and NLS–FGF-2 (as a control). Both proteins showed the same affinity as wild-type FGF-2 for immobilized heparin (data not shown). The mitogenic activities of FGF-2 and NLS-FGF-2 were comparable (Fig. 5a); however, fusion of the NLS to Nb1a2 strongly enhanced its mitogenic activity, which reached roughly 60% of the value obtained with wild-type FGF-2. The fractionation of NIH-3T3 cells that had been stimulated or not with NLS–FGF-2 or NLS–Nb1a2 confirmed the ability of these growth factors to be translocated to the nuclear region (Fig. 5b). These results show that the nuclear association of FGF-2 is essential for its mitogenic activity. To investigate further whether Translokin is the mediator of this translocation, we transfected NIH-3T3 cells with small interfering RNA (siRNA) duplexes21 to reduce the expression of endogenous Translokin. After 55 h of transfection with an siRNA targeting Translokin or a scramble, control siRNA, cells were stimulated by HA–FGF-2, collected and fractionated. The Translokin-specific siRNA led to a decrease in Translokin of about 78%, whereas β-actin remained unaffected (Fig. 5c). Immunofluorescence studies showed that siRNA treatment di....

so I don't think "protein import into nucleus, translocation" (which is nucleocytoplasmic transport through the nuclear pore is exactly the correct term for this experiment, but I don't know what is? maybe just localization? or no annotation at all....).

[ValWood]

This process could occur during centrosome insertion into the nuclear envelope, (although I'm not sure exactly how this happens in a closed mitosis). This would make sense for these proteins and from these results. This would rule out the nucleocytoplasmic transport term.

It would err on the side of caution and use an appropriate "localization" term

[pgaudet]

"protein import into nucleus, translocation" was removed.