PSIP1-PPP1R13B (ASPP1) is a single DSSO crosslink in unfractionated U2OS nuclei with no bait; both proteins are nuclear and both are stress-response regulators, so this is declined on evidence depth alone and is the most biologically coherent row in the beat
also called PSIP1-PPP1R13B · LEDGF-ASPP1 · ASPP1 · EBI-20938252
A database lists ASPP1, a protein that helps p53 decide whether a stressed cell should die, as a partner of the nuclear protein LEDGF/PSIP1. Both are nuclear stress-response proteins so the pairing is not far-fetched, but the whole claim is one chemical crosslink seen in one preparation and nobody has ever tested it another way.
The same thing, for a scientist
**Verdict: DECLINED on evidence depth, not on plausibility. Detection method is chemical crosslinking mass spectrometry (DSSO XL-MS) with no bait: both participants are recorded as 'neutral component'** [E1]. One IntAct record, EBI-20938252, from PMID 30021884, host U2OS osteosarcoma, intact-miscore 0.4, annotated to Table S1 and *'interaction detected in: unfractionated nuclei'* - **one preparation, and the least fractionated one** [E1]. PPP1R13B is UniProt Q96KQ4, 1,090 aa, **Cytoplasm [ECO:0000269] and Nucleus [ECO:0000269]**, the apoptosis-stimulating protein of p53 (ASPP1), which enhances TP53 DNA binding and transactivation at proapoptotic promoters [E3]. **This is the most biologically coherent of the thirteen pairs in the beat** and it deserves saying plainly: PSIP1/LEDGF is a stress-response transcriptional coactivator whose UniProt function comment states it *'may play a protective role during stress-induced apoptosis'*, and ASPP1 is a nuclear regulator of apoptotic transcription [E3]. **Two nuclear proteins in overlapping biology, crosslinked in an intact nucleus, is a genuinely interesting row.** It is declined because it is one crosslink, in one fraction, in one osteosarcoma line, with the crosslinked residues unretrieved, no orthogonal method anywhere in IntAct, and no experiment in any haematopoietic cell - and because IntAct has curated **no PSIP1-bait experiment since 2012** [E4], so nobody has asked the question from PSIP1's side in fourteen years.
Why the most plausible row in the beat is still declined, and what that costs
There is a real cost to declining this one and it should be visible.
The coherent story. PSIP1/LEDGF is a transcriptional coactivator with a documented role in stress responses and in protecting cells from stress-induced apoptosis; ASPP1 is a nuclear regulator that directs p53 to proapoptotic promoters 3. A physical proximity between them would place a chromatin tether directly on the apoptotic transcriptional switch. In a disease treated with agents whose therapeutic effect runs through differentiation and apoptosis, that would matter.
Why it is declined anyway. Coherence is not evidence, and this project's standing rule is that an attractive story is a reason for more scepticism, not less. What exists is one crosslink, in the unfractionated preparation rather than in the Triton-insoluble fraction where the paper reports the nuclear share rises to 85% 2, with 58% replicate overlap across the dataset 2, and with the PSM score and residue positions unretrieved 1.
What the decline is NOT. It is not a claim that the pair is false. It is a claim that the record cannot support an entry asserting the interaction, and that the cheapest route to changing that is the supplementary table rather than a new experiment.
The specific thing to do. Open supplemental Tables S1/S2 of PMID 30021884 and read the crosslinked lysine positions and PSM score for EBI-20938252. If the PSIP1 lysine falls in the PWWP domain or the integrase-binding domain, this stops being a floor-level row and becomes a structural constraint on a druggable surface.
| partner a | gene-psip1 |
|---|---|
| partner a uniprot | O75475 |
| partner a length AA | 530 |
| partner b | PPP1R13B |
| partner b uniprot | Q96KQ4 |
| partner b length AA | 1090 |
| verdict | DECLINED |
| adjudicated by | Q129, cycle 92, 2026-09-23 |
| decline strength | the most biologically coherent pair in the beat; declined on evidence depth alone and flagged as the one most worth re-examining if the supplementary table is ever opened |
| source publication pmid | 30021884 |
| source dataset | Fasci 2018 nuclear XL-MS (DSSO, U2OS intact nuclei) |
| detection method | chemical crosslinking mass spectrometry (DSSO XL-MS) |
| experimental role partner | neutral component |
| experimental role psip1 | neutral component |
| bait exists in dataset | false |
| intact miscore | 0.4 |
| n publications | 1 |
| n methods | 1 |
| orthogonal method exists | false |
| compartment mismatch | false |
| biological coherence | high - PSIP1 is a stress-response coactivator that UniProt says may protect against stress-induced apoptosis; ASPP1 directs TP53 to proapoptotic promoters. No null was computed for how common such coherence is, so this is a flag, not support. |
| psip1 bait publications total | 4 |
| psip1 most recent bait publication | PMID 22872640, J Biol Chem, October 2012 |
| druggability | Not assessable from the record, but this is the row where it could change: if the crosslinked PSIP1 lysine falls in the PWWP domain or the integrase-binding domain - the LEDGIN target - the row becomes a constraint on a druggable surface. The positions are in supplemental Table S1 and were not retrieved. |
| absence class | measured-not-searched |
| absence class note | The decisive missing datum is the crosslinked lysine positions and PSM score for EBI-20938252, in supplemental Table S1 of PMID 30021884 and in that paper's PRIDE deposition, neither opened here - an afternoon's work, and for this pair specifically it is worth doing. The separate never-measured absence is that no experiment has used PSIP1 as a bait against ASPP1, in any cell; IntAct records no PSIP1-bait experiment at all since 2012. |
| shown for fusion | NO - nobody has looked in any KMT2A fusion. U2OS osteosarcoma nuclei; no fusion protein present, and PSIP1's relevance here is as the menin-KMT2A chromatin tether. |
| epigenetic readout | none - no histone mark, occupancy or chromatin measurement exists for this pair. |
host cell lines
[ "U2OS osteosarcoma" ]
preparations detected in
[ "unfractionated nuclei" ]
records
[ "EBI-20938252" ]
partner compartments
[ "Cytoplasm [ECO:0000269]", "Nucleus [ECO:0000269]" ]
interface residues a
[]
structures
[]
- If PSIP1 does sit on the p53 apoptotic switch, a LEDGIN or any agent that displaces LEDGF from chromatin could shift the apoptotic threshold in either direction, and a drug intended to dislodge the menin-KMT2A complex would carry an unmeasured effect on how the cell responds to every other cytotoxic agent given alongside it.
- TP53 is typically wild type in infant KMT2A-rearranged ALL, so an intervention that impaired p53-dependent apoptosis would remove one of the few intact tumour-suppressor routes in that disease. That is a reason to measure this axis before targeting PSIP1, not a reason to believe the crosslink.
- Where does the crosslink land on PSIP1? For this pair specifically the answer decides whether the row is discardable or a constraint on the LEDGIN-targeted integrase-binding domain, and it is one supplementary table away.
- Has any study reported a functional link between LEDGF/PSIP1 and the ASPP family? No PubMed query was run in this beat, so the literature is unbounded on this question and a single search could either strengthen the row substantially or leave it exactly where it is.
- Does PSIP1 influence p53-dependent apoptotic transcription in a KMT2A-rearranged cell? TP53 is usually wild type in infant KMT2A-rearranged ALL, which makes the p53 axis more rather than less relevant there, and this graph has no entry connecting the chromatin tether to it.
- E1established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
IntAct curates one record of a PSIP1-PPP1R13B physical association, EBI-20938252, from PMID 30021884. Detection method 'crosslink' (XL-MS), interaction type 'physical association', NO expansion method, host Homo sapiens U2OS osteosarcoma cell. Both PPP1R13B (Q96KQ4) and PSIP1 (O75475) are recorded as 'neutral component' - no bait, no prey. intact-miscore 0.4. Annotations: 'comment (interaction detected in: unfractionated nuclei)' and 'figure legend (Table S1)'. Within this publication PSIP1 has six crosslink partners: GDF5, HSPA8, IGHMBP2, PPP1R13B, SCAF11 and TMEM214. This is the only one of the four PSIP1 rows adjudicated in this beat that is annotated to the unfractionated preparation alone.
IntAct molecular interaction database, REST findInteractions on O75475 (PSIP1), 114 records retrieved 2026-09-23 by Q129 · IntAct (EMBL-EBI) 2026What this evidence cannot show
Read live from IntAct REST on 2026-09-23, not PSICQUIC (rule 93: PSICQUIC returns about 44% of IntAct's PSIP1 rows, so an earlier instrument would not necessarily have seen this row at all). Supplemental Table S1 was not opened, so the crosslinked residue positions and PSM score are unknown. Whether 'unfractionated nuclei only' is weaker than 'fractionated' is an inference from the paper's statement that the nuclear share rises in the insoluble fraction; the paper makes no such claim about individual rows.
Evidence that argues against this (1)
- The unfractionated preparation is the one closest to an intact nucleus, with no detergent step to redistribute proteins, so it can equally be argued to be the most native rather than the least clean. The paper reports 3,936 unique crosslinks from the unfractionated sample at 1% FDR, so it is not a marginal arm of the experiment. Fasci D et al. 2018
- E2established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paper
In isolated intact human U2OS nuclei, Fasci et al. crosslinked with DSSO (250 micromolar, 4 million nuclei/ml) and identified ~8,710 unique crosslinks at 1% FDR overall: 3,936 from the unfractionated preparation with more than 2,300 connecting distinct proteins, and 7,095 from the combined soluble and insoluble fractions with 4,606 connecting distinct proteins. Replicate overlap between two independent biological replicates is ~58%, the reliable detection depth is ~1.5e4 protein copies per cell, and the identifiable-nuclear share of crosslinks rose to 85% in the Triton X-100 insoluble fraction.
Histone Interaction Landscapes Visualized by Crosslinking Mass Spectrometry in Intact Cell Nuclei. · Fasci D, van Ingen H, Scheltema RA, Heck AJR · Molecular & cellular proteomics : MCP 2018What this evidence cannot show
Full text read 2026-09-23 through the PMC HTML route (PMC6166682, 92,127 stripped characters) after fullTextXML returned HTTP 500 and efetch db=pmc returned a body-less document. The strings 'PSIP1', 'LEDGF' and 'PPP1R13B' each appear ZERO times in the paper's text; this row exists only in a supplementary table not opened here. The paper is about histone and nucleosome interaction hot spots, so its validation work - mapping crosslinks onto high-resolution structures of the nucleosome and the pre-60S particle - does not touch this row.
Evidence that argues against this (1)
- The dataset validates well where it can be checked: 97% of crosslinks mapped onto the pre-60S complex fall within the DSSO distance constraint, and the nucleosome mapping resolves known interaction hot spots. That is a strong argument that the method and the FDR control work, and it applies to this row as much as to any other - the objection is depth of support for one pair, not dataset quality. Fasci D et al. 2018
- E3established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
UniProtKB Q96KQ4 is 1,090 aa, primary gene name PPP1R13B, recommended name 'Apoptosis-stimulating of p53 protein 1' (ASPP1). Subcellular location: Cytoplasm [ECO:0000269]; Nucleus [ECO:0000269]. Function: regulator playing a central role in the regulation of apoptosis via its interaction with TP53, enhancing TP53 DNA binding and transactivation on the promoters of proapoptotic genes in vivo. Tissue specificity: reduced expression in breast carcinomas expressing wild-type TP53. PSIP1 (O75475) is 530 aa, Nucleus [ECO:0000269], a transcriptional coactivator involved in neuroepithelial stem cell differentiation and in lens epithelial gene regulation and stress responses, which UniProt states 'may play a protective role during stress-induced apoptosis'.
UniProtKB entries Q96KQ4 (PPP1R13B) and O75475 (PSIP1): primary gene name, sequence length, subcellular location with evidence codes, function and tissue specificity, retrieved 2026-09-23 · UniProt Consortium 2026What this evidence cannot show
UniProt location and function comments are curated pointers, not measurements (rule 91); the cited papers were not opened. The 'both are stress-response proteins' coherence argument is built from two UniProt function comments and no primary reading - it is a reason the row is interesting, not evidence that it is true, and it is exactly the kind of narrative fit that this project's standing rules say should increase scepticism rather than reduce it. No PubMed query was run on PSIP1 and ASPP1 together in this beat, so whether any functional link has been reported is unknown here.
Evidence that argues against this (1)
- ASPP1 and PSIP1 acting in apoptosis does not mean they act together - 'both involved in stress responses' describes a large fraction of the nuclear proteome, and a coherence argument with no base rate is exactly the kind of claim rule 84 says is not a result until its null is written down. No null was computed here. UniProt Consortium 2026
- E4established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
Across all 114 IntAct records touching PSIP1 (O75475), PSIP1 is recorded as the experimental BAIT in 11 rows from only 4 publications - PMIDs 18598942, 22748127, 22773103 and 22872640 - and as PREY in 91 rows from 29 publications. The most recent publication in which PSIP1 is a bait is PMID 22872640, J Biol Chem, October 2012. For comparison, KMT2A (Q03164) is a bait in 96 of 376 rows across 18 publications, the most recent being PMID 25751424, Nat Struct Mol Biol, April 2015.
IntAct molecular interaction database, REST findInteractions on O75475 and Q03164, experimentalRole counted across all records, retrieved 2026-09-23 by Q129 · IntAct (EMBL-EBI) 2026What this evidence cannot show
This bounds IntAct's curation, NOT the literature. A PSIP1-bait or KMT2A-bait experiment published later and not curated by IntAct would be invisible to this count, and no PubMed search was run to check. Publication years were read from an esummary fetch of each PMID during this session, not from memory.
Evidence that argues against this (1)
- PSIP1 and KMT2A have both been intensively studied since those dates, so the absence of curated bait experiments more likely reflects IntAct's curation backlog and a field-wide shift towards ChIP, cryo-EM and degron methods than an absence of pull-downs. Reading these dates as 'nobody has pulled on these proteins' would be a false absence of the kind rule 93 warns about. IntAct (EMBL-EBI) 2026
adjudicates the IntAct PSIP1-PPP1R13B row; DECLINED on evidence depth only - the most biologically coherent pair in the beat and the one most worth re-examining
the two compartment-compatible crosslinks of the five; both declined on depth alone and both resolvable from one supplementary table