ArticleThe Journal of biological chemistry2013
Phosphorylation of KRAB-associated protein 1 (KAP1) at Tyr-449, Tyr-458, and Tyr-517 by nuclear tyrosine kinases inhibits the association of KAP1 and heterochromatin protein 1α (HP1α) with heterochromatin.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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22 citing papers in PubMed, 42 citations in OpenAlex.
- Roles of TIF1β in Leukemic Stem Cell Through SETDB1-Dependent and Independent Mechanisms.Cancer science · 2026Review
- Chromatin modifier Hmga2 promotes adult hematopoietic stem cell function and blood regeneration in stress conditions.The EMBO journal · 2024Article
- TIF1β activates leukemic transcriptional program in HSCs and promotes BCR::ABL1-induced myeloid leukemia.Leukemia · 2024Article
- Acetylation-Mimic Mutation of TRIM28-Lys304 to Gln Attenuates the Interaction with KRAB-Zinc-Finger Proteins and Affects Gene Expression in Leukemic K562 Cells.International journal of molecular sciences · 2023Article
- KAP1 phosphorylation promotes the survival of neural stem cells after ischemia/reperfusion by maintaining the stability of PCNA.Stem cell research & therapy · 2022Article
- Article
- Src-mediated tyrosine phosphorylation of PRC1 and kinastrin/SKAP on the mitotic spindle.Scientific reports · 2021Article
- Desuppression of TGF-β signaling via nuclear c-Abl-mediated phosphorylation of TIF1γ/TRIM33 at Tyr-524, -610, and -1048.Oncogene · 2019Article
- v-Src-driven transformation is due to chromosome abnormalities but not Src-mediated growth signaling.Scientific reports · 2018Article
- Phosphorylation of TRIM28 Enhances the Expression of IFN-β and Proinflammatory Cytokines During HPAIV Infection of Human Lung Epithelial Cells.Frontiers in immunology · 2018Article
- Potential Roles of Intrinsic Disorder in Maternal-Effect Proteins Involved in the Maintenance of DNA Methylation.International journal of molecular sciences · 2017Article
- Src Acts as an Effector for Ku70-dependent Suppression of Apoptosis through Phosphorylation of Ku70 at Tyr-530.The Journal of biological chemistry · 2017Article
- Protective role for lipid modifications of Src-family kinases against chromosome missegregation.Scientific reports · 2016Article
- A novel nuclear Src and p300 signaling axis controls migratory and invasive behavior in pancreatic cancer.Oncotarget · 2016Article
- Hsp90 in Cancer: Transcriptional Roles in the Nucleus.Advances in cancer research · 2016Review
- TRIM28 as a novel transcriptional elongation factor.BMC molecular biology · 2015Review
- Role for Tyrosine Phosphorylation of A-kinase Anchoring Protein 8 (AKAP8) in Its Dissociation from Chromatin and the Nuclear Matrix.The Journal of biological chemistry · 2015Article
- Article
- KAPtain in charge of multiple missions: Emerging roles of KAP1.World journal of biological chemistry · 2014Review
- Src family kinases promote silencing of ATR-Chk1 signaling in termination of DNA damage checkpoint.The Journal of biological chemistry · 2014Article
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Protein tyrosine phosphorylation regulates a wide range of cellular processes at the plasma membrane. Recently, we showed that nuclear tyrosine phosphorylation by Src family kinases (SFKs) induces chromatin structural changes. In this study, we identify KRAB-associated protein 1 (KAP1/TIF1β/TRIM28), a component of heterochromatin, as a nuclear tyrosine-phosphorylated protein. Tyrosine phosphorylation of KAP1 is induced by several tyrosine kinases, such as Src, Lyn, Abl, and Brk. Among SFKs, Src strongly induces tyrosine phosphorylation of KAP1. Nucleus-targeted Lyn potentiates tyrosine phosphorylation of KAP1 compared with intact Lyn, but neither intact Fyn nor nucleus-targeted Fyn phosphorylates KAP1. Substitution of the three tyrosine residues Tyr-449/Tyr-458/Tyr-517, located close to the HP1 binding-motif, into phenylalanine ablates tyrosine phosphorylation of KAP1. Immunostaining and chromatin fractionation show that Src and Lyn decrease the association of KAP1 with heterochromatin in a kinase activity-dependent manner. KAP1 knockdown impairs the association of HP1α with heterochromatin, because HP1α associates with KAP1 in heterochromatin. Intriguingly, tyrosine phosphorylation of KAP1 decreases the association of HP1α with heterochromatin, which is inhibited by replacement of endogenous KAP1 with its phenylalanine mutant (KAP1-Y449F/Y458F/Y517F, KAP1-3YF). In DNA damage, KAP1-3YF repressed transcription of p21. These results suggest that nucleus-localized tyrosine kinases, including SFKs, phosphorylate KAP1 at Tyr-449/Tyr-458/Tyr-517 and inhibit the association of KAP1 and HP1α with heterochromatin.
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