DDX6 - the only protein ever proposed to do for a cell what Tat does for the virus, on the strength of one 2016 paper

[
  "protein-7sk-snrnp",
  "protein-aff1-kmt2a-reciprocal-product",
  "complex-af4-mll-assembles-a-sixteen-component-elongation-machine",
  "gene-aff1"
]

{
  "chronos_mean_kmt2a_rearranged": -0.9149,
  "chronos_mean_other_leukaemia": -0.9228,
  "difference": 0.0078,
  "pan_essentiality_all_lines": -0.7952,
  "selectivity_rank": 10158,
  "rank_denominator": 17728,
  "provenance": "Joined 2026-09-21 from analyses/depmap-kmt2a-selective-scan-full (generated 2026-09-19T10:12:06Z), the project's own genome-wide scan over 11 KMT2A-rearranged and 43 other leukaemia DepMap lines. NOT re-fetched and NOT independent of that scan: every caveat it carries applies here, including that the KMT2A-rearranged arm is a small number of lines drawn from nine individuals, that the rank denominator is 17,728 genes, and that a difference is not a dependency. Added because only 26 of 308 gene entries carried this number, which made any KMT2A-selectivity question answerable for 8% of the corpus.",
  "how_to_read": "A negative difference means MORE required in KMT2A-rearranged lines than in other leukaemia lines. A rank near 17,728 is ANTI-selective. Neither is evidence of a fusion-driven dependency on its own: check pan_essentiality_all_lines before calling anything selective, and note that a paralogue-redundant gene can score near zero for reasons that have nothing to do with this disease - see ana-the-paralogue-redundancy-excuse-is-not-tested-and-my-proxy-decided-the-answer."
}

{
  "CONSTITUTIVE": "CYTOPLASMIC P-BODY, AND IT IS THE BEST-SUPPORTED COMPARTMENT IN THIS TRANCHE BY WEIGHT OF EVIDENCE. UniProt P26196 (fetched live 2026-09-21) carries 'Cytoplasm, P-body' on EIGHT independent ECO:0000269 citations (PubMed:16364915, 16699599, 20616046, 22915799, 25995375, 26184334, 31422817, 32354837), 'Cytoplasm' and 'Nucleus' (both ECO:0000269 PubMed:26184334 and 28216671), 'Cytoplasm, Stress granule' (ECO:0000269 PubMed:26184334), and 'Cytoplasm, Cytoplasmic ribonucleoprotein granule' (ECO:0000250 from P54823), with the note that DDX6 is imported into the nucleus via interaction with EIF4ENIF1/4E-T by a PIGGY-BACK mechanism and relocalises to stress granules upon cellular stress [E_q93_ddx6_loc1].",
  "CONSTITUTIVE_VERSUS_INDUCED_WHICH_IS_WHAT_THIS_BEAT_ASKS_FOR": "CONSTITUTIVE: cytoplasmic P-bodies, eight citations. INDUCED BY STRESS: stress granules. CONDITIONAL ON A CARRIER: the nuclear pool, which is not autonomous - DDX6 has no NLS of its own on the record and enters the nucleus piggy-backed on 4E-T, established directly by a paper titled 'Dual mechanisms regulate the nucleocytoplasmic localization of human DDX6' which shows DDX6 is COMMONLY PRESENT in the nuclei of human-derived cells and departs from the previous shuttling model [E_q93_ddx6_loc2]. So all three compartments for this protein are conditional in different ways, and none of the three has been measured in a leukaemic cell.",
  "AND_ONE_OF_THE_CITATIONS_IS_A_RULE_91_INSTANCE_OF_A_PARTICULAR_KIND": "PubMed:26184334 carries FOUR of P26196's values - Cytoplasm, Nucleus, P-body and Stress granule - and it is an IMMUNOPRECIPITATION AND MASS SPECTROMETRY interactome study of DDX6. It does contain real localisation microscopy, but OF THE INTERACTORS RATHER THAN OF DDX6: NUFIP2, FAM195A/GRAN1 and FAM195B/GRAN2 are shown NOT to be P-body components and to re-localise to stress granules upon stress [E_q93_ddx6_loc3]. So the most heavily used citation on this record is an AP-MS paper whose compartment experiments are about other proteins - the failure tranche 4 reported, here on the entry with otherwise the strongest evidence base.",
  "how_shown": "eight independent P-body studies; a dedicated nucleocytoplasmic-localisation study establishing 4E-T-dependent piggy-back import (PMID 28216671); an IP-MS interactome with stress-granule imaging of the interactors (PMID 26184334)",
  "systems": "human-derived cell lines throughout; none haematopoietic, none leukaemic, none fusion-bearing",
  "node": "localization-igf2bp3-cytoplasmic-rnp-granules-p-bodies-stress-granules"
}

{
  "expressed_in": "UniProt P26196 tissue specificity: 'Abundantly expressed in most tissues' - no lineage information.",
  "measured_in": "human-derived cell lines for the localisation work; mouse oocytes for the P-body-loss-to-storage-domain transition in the adjacent literature. NOTHING haematopoietic.",
  "in_this_disease": "This entry's existing position is that DDX6's proposed role - binding 7SK snRNA and releasing P-TEFb to the AF4/AF4N super elongation complex - rests on one 2016 paper from one laboratory in a low-profile journal. THAT PROPOSED ROLE IS NUCLEAR, and this tranche's finding sharpens the problem: DDX6's overwhelming constitutive address is the cytoplasmic P-body, and its nuclear pool exists only as a 4E-T passenger. So the mechanism that entry describes would have to be carried out by a minority, carrier-dependent nuclear pool, and the original paper does not address the compartment at all.",
  "and_the_adult_progenitor_result_is_the_cell_type_answer": "DDX6 controls the balance between SELF-RENEWAL AND DIFFERENTIATION in adult progenitors in a context-dependent manner, and its suppression gives human and mouse primed embryonic stem cells a differentiation-resistant hyper-pluripotent state [E_q93_ddx6_loc5]. Adult progenitors and ESCs, not blood - but it is a stem-and-progenitor result on a gene this graph holds for an elongation mechanism."
}

{
  "STRESS_IS_THE_CLASSICAL_INDUCED_STATE": "Upon cellular stress DDX6 relocalises to stress granules [E_q93_ddx6_loc1][E_q93_ddx6_loc3]. Constitutive P-body, induced stress granule.",
  "AND_P_BODY_DISSOLUTION_IS_ITSELF_A_FATE_SWITCH_WHICH_IS_THE_STRONGEST_RESULT_IN_THIS_ENTRY": "Suppressing DDX6 endows human and mouse primed embryonic stem cells with a differentiation-resistant 'hyper-pluripotent' state that readily reprograms to a naive preimplantation-like state; DDX6 mediates translational suppression of target mRNAs in P-bodies, and ON LOSS OF DDX6 ACTIVITY P-BODIES DISSOLVE and release mRNAs encoding fate-instructive transcription and chromatin factors back into the ribosome pool, whose increased translation REWIRES THE ENHANCER, HETEROCHROMATIN AND DNA METHYLATION LANDSCAPES of undifferentiated cell types [E_q93_ddx6_loc5]. So the compartment is not a description here - the existence of the condensate is the repression mechanism, and dissolving it changes cell fate through chromatin.",
  "why_that_matters_for_this_graph": "It is a documented route from a CYTOPLASMIC CONDENSATE to a CHROMATIN STATE, in stem and progenitor cells, on a gene this graph already holds. This project's central disease is a differentiation block maintained by a chromatin mechanism, and cell-state-differentiation-block and cell-state-stem-like-self-renewal are both existing nodes. Nobody has tested DDX6 or P-body content in a KMT2A-rearranged blast.",
  "bounded": "No DDX6 localisation, P-body count or stress-granule measurement exists in any leukaemic cell, and nothing under a menin inhibitor."
}

{
  "date": "2026-09-21",
  "tool": "NCBI E-utilities esearch, db=pubmed",
  "run_by": "Q93",
  "queries": [
    {
      "query": "(\"DDX6\"[tiab] OR \"RCK/p54\"[tiab] OR \"p54/RCK\"[tiab])",
      "querytranslation": "\"DDX6\"[Title/Abstract] OR \"RCK/p54\"[Title/Abstract] OR \"p54/RCK\"[Title/Abstract]",
      "count": 329,
      "role": "operand control"
    },
    {
      "query": "(gene clause) AND (twelve-term subnuclear clause)",
      "count": 8,
      "title_check": "0 are DDX6 subnuclear studies: PMIDs 37591798 (prostate-cancer RBP profiling), 37481122 (LSM14B and oocyte maturation), 35107372 (host helicases and SARS-CoV-2), 31588046 (DDX6 and P-body homeostasis, cited here for cell state), 31429620 (phosphorothioate ASOs and P-body assembly), 23608157 (DDX helicases and HIV-1 Rev), 22090346 (nuclear functions of Pat1b), 20075394 (P-body loss and an mRNA storage domain in mouse oocytes).",
      "bound_not_reproducible_as_stored": "NOT REPRODUCIBLE AS STORED, flagged 2026-09-23. This `query` field records a SUMMARY of the search rather than the search: the clause text it names was never written down, so the string cannot be re-run and this bound could not be included in the cycle-71 audit that re-ran 40 of the corpus's other zero-bounds against the live index (all 40 still returned zero). The clauses have deliberately NOT been reconstructed - guessing them would manufacture a query that was never run, which is worse than an abbreviated one because it would look auditable. This flag does not dispute the count or the absence; it records that this particular bound is not independently checkable."
    },
    {
      "query": "(gene clause) AND (nine-term KMT2A/MLL fusion clause)",
      "count": 5,
      "title_check": "PMIDs 42248567, 35078859, 18692687, 17427874, 12946992; none is a localisation measurement.",
      "bound_not_reproducible_as_stored": "NOT REPRODUCIBLE AS STORED, flagged 2026-09-23. This `query` field records a SUMMARY of the search rather than the search: the clause text it names was never written down, so the string cannot be re-run and this bound could not be included in the cycle-71 audit that re-ran 40 of the corpus's other zero-bounds against the live index (all 40 still returned zero). The clauses have deliberately NOT been reconstructed - guessing them would manufacture a query that was never run, which is worse than an abbreviated one because it would look auditable. This flag does not dispute the count or the absence; it records that this particular bound is not independently checkable."
    },
    {
      "query": "(gene clause) AND (localisation clause) AND (fusion clause)",
      "count": 0,
      "bound_not_reproducible_as_stored": "NOT REPRODUCIBLE AS STORED, flagged 2026-09-23. This `query` field records a SUMMARY of the search rather than the search: the clause text it names was never written down, so the string cannot be re-run and this bound could not be included in the cycle-71 audit that re-ran 40 of the corpus's other zero-bounds against the live index (all 40 still returned zero). The clauses have deliberately NOT been reconstructed - guessing them would manufacture a query that was never run, which is worse than an abbreviated one because it would look auditable. This flag does not dispute the count or the absence; it records that this particular bound is not independently checkable."
    }
  ],
  "reading": "Titles and abstracts only; supporting figures not searched (brief rule 80).",
  "absence_class": "never-measured"
}