Nucleolar and spindle-associated protein 1 (NUSAP1) interacts with a SUMO E3 ligase complex during chromosome segregation

Abstract

The mitotic spindle is composed of dynamic microtubules and associated proteins that together direct chromosome movement during mitosis. The spindle plays a vital role in accurate chromosome segregation fidelity and is a therapeutic target in cancer. Nevertheless, the molecular mechanisms by which many spindle-associated proteins function remains unknown. The cleolar andpindle-ssociated rotein NUSAP1 is a microtubule-binding protein implicated in spindle stability and chromosome segregation. We show here that NUSAP1 localizes to dynamic spindle microtubules in a unique chromosome-centric pattern, in the vicinity of overlapping microtubules, during metaphase and anaphase of mitosis. Mass spectrometry-based analysis of endogenous NUSAP1 interacting proteins uncovered a cell cycle-regulated interaction between the RanBP2-RanGAP1-UBC9 SUMO E3 ligase complex and NUSAP1. Like NUSAP1 depletion, RanBP2 depletion impaired the response of cells to the microtubule poison Taxol. NUSAP1 contains a conserved SAP domain (SAF-A/B, Acinus, and PIAS). SAP domains are common among many other SUMO E3s, and are implicated in substrate recognition and ligase activity. We speculate that NUSAP1 contributes to accurate chromosome segregation by acting as a co-factor for RanBP2-RanGAP1-UBC9 during cell division.

NUSAP1 potentiates chemoresistance in glioblastoma through its SAP domain to stabilize ATR

“…42 Previous studies have indicated that NUSAP1 contains an obvious SAP domain at its Nterminus. 15,33 This study demonstrated that ATR bound to the Cterminus of NUSAP1 (Fig. 4h-j).…”

“…Previous studies have demonstrated that NUSAP1 contains an SAP domain. 33 SAP domains are commonly found in many SUMO E3 ligases. SAP domains have also been implicated in substrate recognition and ligase activity.…”

NUSAP1 and KIAA0101 downregulation by neo-adjuvant therapy is associated with better outcome and survival in breast cancer.

“…The under-expression of NUSAP1 seems to sensitize osteosarcoma cells to treatment with taxol, since NUSAP1 interacts with the SUMO E3 ligase complex contributing to adequate chromosomal segregation [45]. In oral squamous cell carcinoma, NUSAP1 knockdown has been observed to potentiate paclitaxelinduced apoptosis [46].…”

Identification of potential crucial genes associated with the pathogenesis and prognosis of pancreatic adenocarcinoma

“…Nucleolar and spindle associated protein 1(NUSAP1) is located in dynamic spindle microtubules at metaphase and anaphase of mitosis with a unique chromosomal central pattern. It interacts with SUMO E3 ligase complex in the process of chromosome separation near overlapping microtubules (44). NUSAP1 siRNA (L-004754-00) inhibited the drug resistance of human prostate cancer cells induced by NUSAP1, which suggested that NUSAP1 may be used as a biomarker of the antitumor activity of galiellalactone (45); however, to the best of our knowledge, there are currently few studies that focus on NUSAP1 in PAAD.…”