hhp1 and hhp2 negative regulation of checkpoint signalling

[ValWood]

Upstream of sid4
(I hadn't explicitly added BP, have done that now)

[ValWood]

• Hhp2 auto-phosphorylates at four residues and is phosphorylated by the
  cyclin-dependent kinase Cdk1 at three additional sites. Func-
  tionally, these phosphorylation events inhibit Hhp2 catalytic
  activity, as phospho-ablating mutants exhibited enhanced
  in vitro kinase activity. PMID:41354344

• In the mitotic checkpoint, Hhp1 and Hhp2 act upstream of
  Dma1, a ubiquitin ligase that inhibits the Hippo-related sep-
  tation initiation network (SIN) (44–49).

• Hhp1 and Hhp2
  inhibit SIN signaling by phosphorylating the SIN SPB scaffold
  protein Sid4 at T275 and S278, creating a docking site for the
  FHA domain of Dma1 (PMID:24055157) (requested PRO for GO-CAM Term issue: sid4-P T275,S278 PROconsortium/PRoteinOntology#363)

• Dma1 then ubiquitinates Sid4 to
  antagonize Plo1 SPB localization, thus inhibiting the SIN
  during the mitotic checkpoint (54).
  (Plo1 is the most upstream activator of SIN)

[ValWood]

Ideally the branch upstream of sid4 (negative regulation of SIN) including dma1 will be
"term: specific branch of mitotic spindle checkpoint" (I need to find out how to call this and how it would link to septation initiation signalling in the ontology)- in the paper they call it "mitotic checkpoint" but we need a more specific label

Maybe
Dma1-mediated mitotic checkpoint signalling
https://www.pombase.org/reference/PMID:30600396

[ValWood]

Curate
https://www.pombase.org/reference/PMID:30600396

We call it
'mitotic spindle assembly checkpoint signalling' here
https://www.pombase.org/reference/PMID:22669973

[PCarme]

Curate
https://www.pombase.org/reference/PMID:30600396

This paper is currently assigned to Alaina Willet, should I re-assign it to myself ?

[ValWood]

Actually, it isn't one of Alaina's so I deleted the session. You can take it instead!
v

[PCarme]

We call it
'mitotic spindle assembly checkpoint signalling' here
https://www.pombase.org/reference/PMID:22669973

We have a model for 'mitotic spindle assembly checkpoint signalling', but dma1 is not modelled in it (although it is annotated to the term). It seems to be the correct term, as one of its synonyms is 'Dma1-dependent checkpoint'.
Should hhp1 and 2 be annotated to that term?

[ValWood]

It's a separate branch of the checkpoint, we need to find out exactly what is upstream.
For the spindle checkpoint people only usually think of the part that inhibits chromosome separation through the APC but this is linking the 'spindle checkpoint module' to the SIN (so it should probably be a linking entity upstream of the SIN, and in the checkpoint model too).

[ValWood]

OK, it doesn' link to the spindle assembly checkpoint at all. It's not a branch, its a completely parallel pathway according to AI:

In Schizosaccharomyces pombe, the pathway involving Dma1 is generally called the:
Cytokinesis checkpoint
or more specifically the SIN inhibitory checkpoint
or Dma1-dependent checkpoint

I think for now, just model as negative regulation of SIN.

When I review the cell cycle GO terms I'll consider renaming the "negative regulation of SIN" as a checkpoint.
There is another checkpoint in G2 named
GO:0044878 mitotic cytokinesis checkpoint signaling
but this operates in G2 and monitors cytokinesis completion
So we need to be careful with the naming.

Eventually, I would like the "negative regulation of blah" signalling pathways for cell cycle control to have appropriate signalling pathway/checkpoint terms. Because at the moment we have a weird situation where "negative regulation of signalling" isn't an is_a signalling !

[ValWood]

I changed
dma1 in PMID:22669973
to
| GO:0031030 | negative regulation of septation initiation signaling

[PCarme]

Actually, it isn't one of Alaina's so I deleted the session. You can take it instead! v

I checked this paper, it's a mini-review, there is nothing to curate there. And all the papers they cite related to Hhp1/2's involvement in this checkpoint are already curated