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Article: Dissecting The Novel Partners Of Nuclear C-raf And Its Role In All-trans Retinoic Acid (atra)-induced Myeloblastic Leukemia Cells Differentiation

TitleDissecting The Novel Partners Of Nuclear C-raf And Its Role In All-trans Retinoic Acid (atra)-induced Myeloblastic Leukemia Cells Differentiation
Authors
KeywordsATRA
APL
Cyclin-dependent kinase 2
RB
SMARCD1
Issue Date2020
PublisherAcademic Press. The Journal's web site is located at http://www.elsevier.com/locate/yexcr
Citation
Experimental Cell Research, 2020, Epub 2020-04-10 How to Cite?
AbstractAll-trans retinoic acid (ATRA) is an anti-cancer differentiation therapy agent effective for acute promyelocytic leukemia (APL) but not acute myeloid leukemia (AML) in general. Using the HL-60 human non-APL AML model where ATRA causes nuclear enrichment of c-Raf that drives differentiation and G1/G0 cell cycle arrest, we now observe that c-Raf in the nucleus showed novel interactions with several prominent regulators of the cell cycle and cell differentiation. One is cyclin-dependent kinase 2 (Cdk2). ATRA treatment caused c-Raf to dissociate from Cdk2. This was associated with enhanced binding of Cdk2 with retinoic acid receptor α (RARα). Consistent with this novel Raf/CDK2/RARα axis contributing to differentiation, CD38 expression per cell, which is transcriptionally regulated by a retinoic acid response element (RARE), is enhanced. The RB tumor suppressor, a fundamental regulator of G1 cell cycle progression or arrest, was also targeted by c-Raf in the nucleus. RB and specifically the S608 phosphorylated form (pS608RB) complexed with c-Raf. ATRA treatment induced S608RB-hypophosphorylation associated with G1/G0 cell cycle arrest and release of c-Raf from RB. We also found that nuclear c-Raf interacted with SMARCD1, a pioneering component of the SWI/SNF chromatin remodeling complex. ATRA treatment diminished the amount of this protein bound to c-Raf. The data suggest that ATRA treatment to HL-60 human cells re-directed c-Raf from its historically pro-proliferation functions in the cytoplasm to pro-differentiation functions in the nucleus.
Persistent Identifierhttp://hdl.handle.net/10722/283754
ISSN
2023 Impact Factor: 3.3
2023 SCImago Journal Rankings: 0.947
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorRashid, A-
dc.contributor.authorWang, R-
dc.contributor.authorZhang, L-
dc.contributor.authorYue, J-
dc.contributor.authorYang, M-
dc.contributor.authorYen, A-
dc.date.accessioned2020-07-03T08:23:36Z-
dc.date.available2020-07-03T08:23:36Z-
dc.date.issued2020-
dc.identifier.citationExperimental Cell Research, 2020, Epub 2020-04-10-
dc.identifier.issn0014-4827-
dc.identifier.urihttp://hdl.handle.net/10722/283754-
dc.description.abstractAll-trans retinoic acid (ATRA) is an anti-cancer differentiation therapy agent effective for acute promyelocytic leukemia (APL) but not acute myeloid leukemia (AML) in general. Using the HL-60 human non-APL AML model where ATRA causes nuclear enrichment of c-Raf that drives differentiation and G1/G0 cell cycle arrest, we now observe that c-Raf in the nucleus showed novel interactions with several prominent regulators of the cell cycle and cell differentiation. One is cyclin-dependent kinase 2 (Cdk2). ATRA treatment caused c-Raf to dissociate from Cdk2. This was associated with enhanced binding of Cdk2 with retinoic acid receptor α (RARα). Consistent with this novel Raf/CDK2/RARα axis contributing to differentiation, CD38 expression per cell, which is transcriptionally regulated by a retinoic acid response element (RARE), is enhanced. The RB tumor suppressor, a fundamental regulator of G1 cell cycle progression or arrest, was also targeted by c-Raf in the nucleus. RB and specifically the S608 phosphorylated form (pS608RB) complexed with c-Raf. ATRA treatment induced S608RB-hypophosphorylation associated with G1/G0 cell cycle arrest and release of c-Raf from RB. We also found that nuclear c-Raf interacted with SMARCD1, a pioneering component of the SWI/SNF chromatin remodeling complex. ATRA treatment diminished the amount of this protein bound to c-Raf. The data suggest that ATRA treatment to HL-60 human cells re-directed c-Raf from its historically pro-proliferation functions in the cytoplasm to pro-differentiation functions in the nucleus.-
dc.languageeng-
dc.publisherAcademic Press. The Journal's web site is located at http://www.elsevier.com/locate/yexcr-
dc.relation.ispartofExperimental Cell Research-
dc.subjectATRA-
dc.subjectAPL-
dc.subjectCyclin-dependent kinase 2-
dc.subjectRB-
dc.subjectSMARCD1-
dc.titleDissecting The Novel Partners Of Nuclear C-raf And Its Role In All-trans Retinoic Acid (atra)-induced Myeloblastic Leukemia Cells Differentiation-
dc.typeArticle-
dc.identifier.emailRashid, A: arashid2@hku.hk-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/j.yexcr.2020.111989-
dc.identifier.pmid32283065-
dc.identifier.scopuseid_2-s2.0-85086332415-
dc.identifier.hkuros310703-
dc.identifier.volumeEpub 2020-04-10-
dc.identifier.isiWOS:000560535300001-
dc.publisher.placeUnited States-
dc.identifier.issnl0014-4827-

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