NPM1
GeneName
NPM1
Summary
NPM1, also known as NPM or nucleophosmin, is a 33kDa nucleolar protein that is predominantly expressed in the nucleolus and nucleoplasm, with additional presence in the cytoplasm and centrosome. It plays a multifaceted role in various cellular processes, including chromatin remodelling, ribosome biogenesis, and the regulation of the cell cycle. NPM1 is involved in binding to DNA and RNA, functioning as a transcription coactivator and a molecular adaptor. It also participates in the cellular response to stress and DNA damage, and is implicated in the regulation of apoptotic processes and cell volume homeostasis.
Importance
NPM1 is relevant to: - Cancer research, particularly in acute myeloid leukaemia, where mutations in NPM1 are frequently observed and associated with disease progression. - Understanding nucleolar function and dynamics, given its central role in ribosome assembly and protein synthesis. - Investigating cellular stress responses and the mechanisms of cellular senescence, as it is involved in the regulation of apoptosis and cell cycle progression. - Exploring its function in centrosome duplication and microtubule organisation, which are critical for proper cell division and maintaining genomic stability.
Top Products
For researchers investigating NPM1, we recommend two excellent primary antibodies. The first is the well-cited Anti-Nucleophosmin antibody [FC82291] (ab10530), a trusted monoclonal antibody that has garnered 124 citations. It is particularly effective for Western blotting (WB) and immunocytochemistry (ICC), making it a reliable choice for your experiments. Additionally, we offer the recombinant Anti-Nucleophosmin antibody [EP1848Y] (ab52644), which has been validated for use in a broader range of applications, including WB, ICC, immunohistochemistry (IHC), and flow cytometry (FC). With 15 citations, this recombinant antibody provides the batch-to-batch consistency that many researchers seek. Together, these antibodies provide robust options for studying NPM1 in various experimental contexts.
Abcam Product Citation Summary
The data indicates that NPM1 is frequently studied in the context of human cancer, particularly breast carcinoma and T-cell leukemia. The use of Abcam antibodies in various applications such as Western blotting and immunofluorescence highlights the importance of NPM1 in cell cycle dynamics and cancer research. Additionally, studies involving human cell lines and tissues suggest a significant role of NPM1 in cancer biology.
Abcam Product Citation Table
Function
Involved in diverse cellular processes such as ribosome biogenesis, centrosome duplication, protein chaperoning, histone assembly, cell proliferation, and regulation of tumor suppressors p53/TP53 and ARF. Binds ribosome presumably to drive ribosome nuclear export. Associated with nucleolar ribonucleoprotein structures and bind single-stranded nucleic acids. Acts as a chaperonin for the core histones H3, H2B and H4. Stimulates APEX1 endonuclease activity on apurinic/apyrimidinic (AP) double-stranded DNA but inhibits APEX1 endonuclease activity on AP single-stranded RNA. May exert a control of APEX1 endonuclease activity within nucleoli devoted to repair AP on rDNA and the removal of oxidized rRNA molecules. In concert with BRCA2, regulates centrosome duplication. Regulates centriole duplication: phosphorylation by PLK2 is able to trigger centriole replication. Negatively regulates the activation of EIF2AK2/PKR and suppresses apoptosis through inhibition of EIF2AK2/PKR autophosphorylation. Antagonizes the inhibitory effect of ATF5 on cell proliferation and relieves ATF5-induced G2/M blockade (PubMed:22528486). In complex with MYC enhances the transcription of MYC target genes (PubMed:25956029). May act as chaperonin or cotransporter in the nucleolar localization of transcription termination factor TTF1 (By similarity).
Involvement in disease
A chromosomal aberration involving NPM1 is found in a form of non-Hodgkin lymphoma. Translocation t(2;5)(p23;q35) with ALK. The resulting chimeric NPM1-ALK protein homodimerize and the kinase becomes constitutively activated.
A chromosomal aberration involving NPM1 is found in a form of acute promyelocytic leukemia. Translocation t(5;17)(q32;q11) with RARA.
A chromosomal aberration involving NPM1 is a cause of myelodysplastic syndrome (MDS). Translocation t(3;5)(q25.1;q34) with MLF1.
Defects in NPM1 are associated with acute myelogenous leukemia (AML). Mutations in exon 12 affecting the C-terminus of the protein are associated with an aberrant cytoplasmic location.
Post-translational modifications
Acetylated at C-terminal lysine residues, thereby increasing affinity to histones.
ADP-ribosylated.
Phosphorylated at Ser-4 by PLK1 and PLK2. Phosphorylation at Ser-4 by PLK2 in S phase is required for centriole duplication and is sufficient to trigger centriole replication. Phosphorylation at Ser-4 by PLK1 takes place during mitosis. Phosphorylated by CDK2 at Ser-125 and Thr-199. Phosphorylation at Thr-199 may trigger initiation of centrosome duplication. Phosphorylated by CDK1 at Thr-199, Thr-219, Thr-234 and Thr-237 during cell mitosis. When these four sites are phosphorated, RNA-binding activity seem to be abolished. May be phosphorylated at Ser-70 by NEK2. The Thr-199 phosphorylated form has higher affinity for ROCK2. CDK6 triggers Thr-199 phosphorylation when complexed to Kaposi's sarcoma herpesvirus (KSHV) V-cyclin, leading to viral reactivation by reducing viral LANA levels.
Sumoylated by ARF.
Ubiquitinated. Ubiquitination leads to proteasomal degradation. Deubiquitinated by USP36 (PubMed:19208757).
Sequence Similarities
Belongs to the nucleoplasmin family.
Cellular localization
- Nucleus
- Nucleolus
- Nucleus
- Nucleoplasm
- Cytoplasm
- Cytoskeleton
- Microtubule organizing center
- Centrosome
- Generally nucleolar, but is translocated to the nucleoplasm in case of serum starvation or treatment with anticancer drugs. Has been found in the cytoplasm in patients with primary acute myelogenous leukemia (AML), but not with secondary AML. Co-localizes with the methylated form of RPS10 in the granular component (GC) region of the nucleolus. Colocalized with nucleolin and APEX1 in nucleoli. Isoform 1 of NEK2 is required for its localization to the centrosome during mitosis. Can shuttle between cytoplasm and nucleus (PubMed:38231884).
Alternative names
NPM, NPM1, Nucleophosmin, Nucleolar phosphoprotein B23, Nucleolar protein NO38, Numatrin