Optical two-dimensional coherent spectroscopy of cold atoms.

We report an experimental demonstration of optical two-dimensional coherent spectroscopy (2DCS) in cold atoms. The experiment integrates a collinear 2DCS setup with a magneto-optical trap (MOT), in which cold rubidium (Rb) atoms are prepared at a temperature of approximately 200 µK and a number density of 1010 cm-3. With a sequence of femtosecond laser pulses, we first obtain one-dimensional second- and fourth-order nonlinear signals and then acquire both one-quantum and zero-quantum 2D spectra of cold Rb atoms. The capability of performing optical 2DCS in cold atoms is an important step toward optical 2DCS study of many-body physics in cold atoms and ultimately in atom arrays and trapped ions. Optical 2DCS in cold atoms/molecules can also be a new avenue to probe chemical reaction dynamics in cold molecules.

Stub1 maintains proteostasis of master transcription factors in embryonic stem cells.

The pluripotency and differentiation states of embryonic stem cells (ESCs) are regulated by a set of core transcription factors, primarily Sox2, Oct4, and Nanog. Although their transcriptional regulation has been studied extensively, the contribution of posttranslational modifications in Sox2, Oct4, and Nanog are poorly understood. Here, using a CRISPR-Cas9 knockout library screen in murine ESCs, we identify the E3 ubiquitin ligase Stub1 as a negative regulator of pluripotency. Manipulation of Stub1 expression in murine ESCs shows that ectopic Stub1 expression significantly reduces the protein half-life of Sox2, Oct4, and Nanog. Mechanistic investigations reveal Stub1 catalyzes the polyubiquitination and 26S proteasomal degradation of Sox2 and Nanog through K48-linked ubiquitin chains and Oct4 via K63 linkage. Stub1 deficiency positively enhances somatic cell reprogramming and delays differentiation, whereas its enforced expression triggers ESC differentiation. The discovery of Stub1 as an integral pluripotency regulator strengthens our understanding of ESC regulation beyond conventional transcriptional control mechanisms.

TRIM27 cooperates with STK38L to inhibit ULK1-mediated autophagy and promote tumorigenesis.

Autophagy represents a fundamental mechanism for maintaining cell survival and tissue homeostasis in response to physiological and pathological stress. Autophagy initiation converges on the FIP200-ATG13-ULK1 complex wherein the serine/threonine kinase ULK1 plays a central role. Here, we reveal that the E3 ubiquitin ligase TRIM27 functions as a negative regulatory component of the FIP200-ATG13-ULK1 complex. TRIM27 directly polyubiquitinates ULK1 at K568 and K571 sites with K48-linked ubiquitin chains, with proteasomal turnover maintaining control over basal ULK1 levels. However, during starvation-induced autophagy, TRIM27 catalyzes non-degradative K6- and K11-linked ubiquitination of the serine/threonine kinase 38-like (STK38L) kinase. In turn, STK38L ubiquitination promotes its activation and phosphorylation of ULK1 at Ser495, rendering ULK1 in a permissive state for TRIM27-mediated hyper-ubiquitination of ULK1. This cooperative mechanism serves to restrain the amplitude and duration of autophagy. Further evidence from mouse models shows that basal autophagy levels are increased in Trim27 knockout mice and that Trim27 differentially regulates tumorigenesis and metastasis. Our study identifies a key role of STK38L-TRIM27-ULK1 signaling axis in negatively controlling autophagy with relevance established in human breast cancer.

Lotus seedpods biochar decorated molybdenum disulfide for portable, flexible, outdoor and inexpensive sensing of hyperin.

Biomass waste, a good candidate for advanced carbon materials for sustainable electrodes, is receiving more and more attention for high value-added materials because of its promising contribution to economic growth and sustainable development. We proposed a green co-hydrothermal approach to prepare lotus seedpods biochar (BC) decorated molybdenum disulfide (MoS2) from waste lotus seedpods and precursors of MoS2, and a portable, flexible, outdoor and inexpensive sensing platform for hyperin on the integrated flexible three-electrode using U-disk potentiostat with smartphone was successfully developed. Structure and properties of MoS2-BC were characterized, it was proved that BC improves microstructure and morphology, electronic conductivity, electrode stability and electrocatalytic properties of MoS2. Attributing to these impressive features, the detection signal of hyperin was significantly amplified by the MoS2-BC modified glass carbon electrode (GCE) in detection range of 0.01-21 µΜ with detection limit (LOD) of 5 nM. It was worth mentioning that the MoS2-BC modified screen-printed electrode (SPE) performs hyperin detection in range of 100 nM - 3 µM with LOD 50 nM (S/N = 3). The practicability of the proposed method confirmed that the portable, on-site, low-cost, and outdoor detection of hyperin was feasible and practical in comparison with traditional both electrochemical sensing and HPLC methods.

Collective Resonance of D States in Rubidium Atoms Probed by Optical Two-Dimensional Coherent Spectroscopy.

Collective resonance of interacting particles has important implications in many-body quantum systems and their applications. Strong interactions can lead to a blockade that prohibits the excitation of a collective resonance of two or more nearby atoms. However, a collective resonance can be excited with the presence of weak interaction and has been observed for atoms in the first excited state (P state). Here, we report the observation of collective resonance of rubidium atoms in a higher excited state (D state) in addition to the first excited state. The collective resonance is excited by a double-quantum four-pulse excitation sequence. The resulting double-quantum two-dimensional (2D) spectrum displays well-isolated peaks that can be attributed to collective resonances of atoms in P and D states. The experimental one-quantum and double-quantum 2D spectra can be reproduced by a simulation based on the perturbative solutions to the optical Bloch equations, confirming collective resonances as the origin of the measured spectra. The experimental technique provides a new approach for preparing and probing collective resonances of atoms in highly excited states.

Interaction-free bidirectional multi-channel all-optical switching in a multi-level coupling atom-cavity system.

We propose a scheme of interaction-free bidirectional multi-channel all-optical switching in a multi-level coupling system consisting of four-level atoms confined in a cavity and coupled by a free-space control laser. A signal laser field is coupled into the cavity and excites two separate transitions of atoms simultaneously under the collective strong coupling condition. The transmission and reflection of signal fields form bidirectional output channels. A free-space control laser induces destructive quantum interference in the multi-level excitation of an atom-cavity system, which can be used to switch on/off the output signal lights of transmission/reflection channels. There is no direct coupling of control light and signal light through the cavity-confined atoms because the output of signal light is nearly totally suppressed to the opposite direction when control light is present. The proposed all-optical switching scheme can be realized with high switching efficiency, broad bandwidth, and weak light intensity. It may be useful for future devices of optical routing, optical communications, and various quantum logic elements.

Green synthesis of kudzu vine biochar decorated graphene-like MoSe2 with the oxidase-like activity as intelligent nanozyme sensing platform for hesperetin.

It is an urgent need to exploit a potentially green, cost efficient and eco-friendly strategy for the utilization of waste kudzu vine. We developed a one-step green preparation of kudzu vine biochar (BC) decorated graphene-like molybdenum selenide (MoSe2) with the oxidase-like activity as intelligent nanozyme sensing platform for voltametric detection of hesperetin (HP) in orange peel using the in-situ hydrothermal synthesis method. The structure and properties of MoSe2-BC was characterized, and found that BC significantly improved electrochemical cycle stability, electronic conductivity, electrochemical active area, and electrocatalytic activity of MoSe2. The oxidase-like activity of MoSe2-BC was confirmed by the oxidization of the colorless substrate 3,3',5,5'-tetramethylbenzidine (TMB) to form blue products and the change of absorbance intensity of UV-vis absorption spectra. The MoSe2-BC exhibited excellent electrochemical sensing performance for the detection of HP in wide linear ranges from 10 nM to 9.5 µM with a low limit of detection of 2 nM using differential pulse voltammetric method. An emerging machine learning technique is used to realize the intelligent sensing of HP, and the performance evaluation of regression analysis was selected to evaluate this technique. This work will provide a guidance for the preparation and application of biochar decorated graphene-like nanomaterials with the oxidase-like activity and the development of intelligent nanozyme sensing platform.

Biased gene expression reveals the contribution of subgenome to altitude adaptation in allopolyploid Isoetes sinensis.

Allopolyploids are believed to inherit the genetic characteristics of its progenitors and exhibit stronger adaptability and vigor. The allotetraploid Isoetes sinensis was formed by the natural hybridization and polyploidization of two diploid progenitors, Isoetes taiwanensis and Isoetes yunguiensis, and was believed to have the potential to adapt to plateau environments. To explore the expression pattern of homoeologous genes and their contributions to altitude adaptation, we transplanted natural allotetraploid I. sinensis (TnTnYnYn) along the altitude gradient for a long-term, and harvested them in summer and winter, respectively. One year after transplanting, it still lived well, even in the extreme environment of the Qinghai-Tibet Plateau. Then, we performed high-throughput RNA sequencing to measure their gene expression level. A total of 7801 homoeologous genes were expressed, among which 5786 were identified as shared expression in different altitudes and seasons. We further found that altitude variations could change the subgenome bias trend of I. sinensis, but season could not. Moreover, the functions of uniquely expressed genes indicated that temperature might be an important restrictive factor during the adaptation process. Through the analysis of DEGs and uniquely expressed genes, we found that Y subgenome provided more contributions to high altitude adaptation than T subgenome. These adaptive traits to high altitude may be inherited from its plateau progenitor I. yunguiensis. Through weighted gene co-expression network analysis, pentatricopeptide repeats gene family and glycerophospholipid metabolism pathway were considered to play important roles in high-altitude adaptation. Totally, this study will enrich our understanding of allopolyploid in environmental adaptation.

A portable wireless intelligent electrochemical sensor based on layer-by-layer sandwiched nanohybrid for terbutaline in meat products.

The aim of this study is to develop a portable wireless intelligent nanosensor (PWIN) for rapid cost-effective on-site determination of terbutaline (TRA) residue in meat products outdoors in comparison with traditional nanosensor and high-performance liquid chromatography (HPLC). The layer-by-layer sandwiched nanohybrid fabricated by platinum-palladium nanoparticles, carboxylated graphene and graphene-like molybdenum disulfide displayed a wide linear range of 0.55-14.9 µmol/L using the portable potentiostat with smartphone, and the result was almost close to the linear range (0.4-14 µmol/L) using the traditional potentiostat with desktop computer for TRA. The limit of detections were identified as 0.44 µmol/L and 0.18 µmol/L, respectively. PWIN displayed satisfactory recovery (91%-98.43%) of TRA in samples by the standard addition method and in comparison with both traditional sensor (93.79%-98%) and HPLC (93.4%-98.6%), revealing that PWIN for rapid cost-effective on-site analysis in the food safety field is feasible.

Portable wireless intelligent sensing of ultra-trace phytoregulator α-naphthalene acetic acid using self-assembled phosphorene/Ti3C2-MXene nanohybrid with high ambient stability on laser induced porous graphene as nanozyme flexible electrode.

The harm of pesticide residues to human health via environmental pollution in agriculture has recently become a significant livelihood issue. Herein, a new strategy for smart ultra-trace analysis of phytoregulator α-naphthalene acetic acid (NAA) residues in farmland environments and agro-products via machine learning (ML) using a nanozyme flexible electrode fabricated by two-dimensional phosphorene (BP) nanohybrid with graphene-like titanium carbide MXene (Ti3C2-MXene) on the flexible substrate surface of laser-induced porous graphene (LIPG) is proposed. Highly ambient-stable BP nanohybrid with Ti3C2-MXene is prepared by ultrasonic-assisted liquid-phase exfoliation in organic solvent containing grinding black phosphorus, cuprous chloride and, Ti3C2-MXene that is obtained by selectively etching Al layers of Ti3AlC2. Nanozyme flexible electrode is fabricated by drop-coating Ti3C2-MXene/BP that is formed through electrostatic self-assembly between positively charged BP and negatively charged Ti3C2-MXene onto LIPG that is obtained by direct laser writing on commercial polyimide and patterned via a computer-aided design system as a flexible substrate. The ML model via artificial neural network algorithm for smart output of NAA is discussed. NAA is electrochemically detected in a wide linear range of 0.02-40 µM with a low limit of detection (LOD) of 1.6 nM using a portable mini-workstation. Large and rough surfaces, excellent electrochemical response, and satisfactory practicability demonstrated the feasibility and detectability of the proposed method. This will provide a portable wireless intelligent nanozyme flexible sensing platform for cost-effective, simple, fast and, ultra-trace detection of hazardous substances in the safety of environments, products, and food in agriculture.

A highly-sensitive and selective antibody-like sensor based on molecularly imprinted poly(L-arginine) on COOH-MWCNTs for electrochemical recognition and detection of deoxynivalenol.

A new strategy to mimic antibody for electrochemical recognition and detection of deoxynivalenol (DON) using a highly-sensitive and selective antibody-like sensor based on molecularly imprinted poly(l-arginine) (P-Arg-MIP) on carboxylic acid functionalized carbon nanotubes (COOH-MWCNTs) was proposed. l-arginine as functional monomer was screened to prepare imprinted electrode via its electro-polymerization in the presence of DON onto the surface of COOH-MWCNTs electrode coupled with theoretical calculation. Surface morphology, structural characteristics, and electrochemical properties of P-Arg-MIP/COOH-MWCNTs were characterized by SEM, EDS, FTIR, and CV, respectively. P-Arg-MIP/COOH-MWCNTs displayed relatively high conductivity, high effective surface area, antibody-like molecular recognition and affinity, and a good response towards DON in a linear range from 0.1 to 70 µM with LOD of 0.07 µM in wheat flour samples with satisfactory recovery and feasible practicability in comparison with HPLC. This method provides a promising biomimetic sensing platform for the determination of mycotoxins in food and agro-products.

KDM6A promotes imatinib resistance through YY1-mediated transcriptional upregulation of TRKA independently of its demethylase activity in chronic myelogenous leukemia.

Rationale: Despite landmark therapy of chronic myelogenous leukemia (CML) with tyrosine kinase inhibitors (TKIs), drug resistance remains problematic. Cancer pathogenesis involves epigenetic dysregulation and in particular, histone lysine demethylases (KDMs) have been implicated in TKI resistance. We sought to identify KDMs with altered expression in CML and define their contribution to imatinib resistance. Methods: Bioinformatics screening compared KDM expression in CML versus normal bone marrow with shRNA knockdown and flow cytometry used to measure effects on imatinib-induced apoptosis in K562 cells. Transcriptomic analyses were performed against KDM6A CRISPR knockout/shRNA knockdown K562 cells along with gene rescue experiments using wildtype and mutant demethylase-dead KDM6A constructs. Co-immunoprecipitation, luciferase reporter and ChIP were employed to elucidate mechanisms of KDM6A-dependent resistance. Results: Amongst five KDMs upregulated in CML, only KDM6A depletion sensitized CML cells to imatinib-induced apoptosis. Re-introduction of demethylase-dead KDM6A as well as wild-type KDM6A restored imatinib resistance. RNA-seq identified NTRK1 gene downregulation after depletion of KDM6A. Moreover, NTRK1 expression positively correlated with KDM6A in a subset of clinical CML samples and KDM6A knockdown in fresh CML isolates decreased NTRK1 encoded protein (TRKA) expression. Mechanistically, KDM6A was recruited to the NTRK1 promoter by the transcription factor YY1 with subsequent TRKA upregulation activating down-stream survival pathways to invoke imatinib resistance. Conclusion: Contrary to its reported role as a tumor suppressor and independent of its demethylase function, KDM6A promotes imatinib-resistance in CML cells. The identification of the KDM6A/YY1/TRKA axis as a novel imatinib-resistance mechanism represents an unexplored avenue to overcome TKI resistance in CML.

Multiwalled Carbon Nanotube-N-Doped Graphene/Poly(3,4-ethylenedioxythiophene):Poly(styrenesulfonate) Nanohybrid for Electrochemical Application in Intelligent Sensors and Supercapacitors.

In this study, we reported the preparation of a conducting polymeric/inorganic nanohybrid consisting of multiwalled carbon nanotubes (MWCNT), N-doped graphene (NGr), and poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS), and its electrochemical application in intelligent sensors and supercapacitors. The multilayer thin film of the PEDOT:PSS-supported MWCNT-NGr nanohybrid was prepared by a facile layer-by-layer assembly strategy. The obtained conducting polymeric/inorganic nanohybrid modified electrode displayed superior electron transfer ability and a high specific surface area, which was used for electrochemical applications in intelligent sensors and supercapacitors. Remarkably, the fabricated amaranth sensor exhibited a broad linear range of 0.05-10 µM with a limit of detection of 0.015 µM under the optimal conditions. With the help of the response surface methodology, multivariate optimization was used as a substitute for the traditional single variable optimization to reflect the complete real effects of multivariate optimization in a sensing platform. Machine learning implemented by hybrid genetic algorithm-artificial neural network was used as an intelligent analysis model to replace the traditional regression analysis model for realizing intelligent analysis and output of sensing system. The MWCNT-NGr/PEDOT:PSS modified electrode exhibited a considerable specific capacitance of 6.5 mF cm-2 at a current density of 2.0 mA cm-2. The proposed results provided a new thought for a nanosensing platform equipped with a supercapacitor as a self-powered electrochemical energy storage system and machine learning as an intelligent analysis and output system in the near future.

Convergence and divergence focusing phenomena at the focal plane of ultrashort pulses.

Using the Richards-Wolf diffraction integral theory and the tightly focused ultrashort pulse vector model, the focusing phenomena at the focal plane of subcycle and few-cycle radially polarized ultrashort pulses are studied. The dynamic focusing is revealed at the focal plane. First, the subcycle or few-cycle ultrashort pulses shrink towards the focus. Then the ultrashort pulses diverge from the focus. So, the convergence and divergence moving halo at the focal plane can be observed. When approaching the focus, the amplitude of the pulse becomes larger. The phenomena can be understood from the Huygens-Fresnel principle and are important for applications of the focused ultrashort pulses.

Long range dipole-dipole interaction in low-density atomic vapors probed by double-quantum two-dimensional coherent spectroscopy.

Optical double-quantum two-dimensional coherent spectroscopy (2DCS) was implemented to probe interatomic dipole-dipole interactions in both potassium and rubidium atomic vapors. The dipole-dipole interaction was detected at densities of 4.81×108 cm -3 and 8.40×109 cm -3 for potassium and rubidium, respectively, corresponding to a mean interatomic separation of 15.8 µm or 3.0×105 a 0 for potassium and 6.1 µm or 1.2×105 a 0 for rubidium, where a 0 is the Bohr radius. The experimental results confirm the long range nature of the dipole-dipole interaction, which is critical for understanding many-body physics in atoms/molecules. The long range interaction also has implications in atom-based applications involving many-body interactions. Additionally, we demonstrated that double-quantum 2DCS is sufficiently sensitive to probe dipole-dipole interaction at densities that can be achieved with cold atom in a magneto-optical trap, paving the way for double-quantum 2DCS studies of cold atoms and molecules. The method can also open a new avenue to study long-range interactions in solid state systems such as quantum dots and color centers in diamonds.

In-situ reduction of Ag+ on black phosphorene and its NH2-MWCNT nanohybrid with high stability and dispersibility as nanozyme sensor for three ATP metabolites.

The environmental stability, water-processibility and life-span of black phosphorene (BP) severely limit the application of its electronic devices in aqueous system containing oxygen. We reported the controllable preparation of in-situ reduction and deposition of silver nanoparticles on the BP surface and its amino-functionalized multi-walled carbon nanotubes (NH2-MWCNT) nanocomposite. With the addition of both NH2-MWCNT and Ag+, the BP-based nanocomposite was prepared by ultrasonic-assisted liquid-phase exfoliation and was dispersed in carboxymethyl cellulose sodium (CMC) aqueous solution. The morphology, microstructure, and electrochemical properties of the nanohybrid were characterized. NH2-MWCNT-BP-AgNPs showed high environmental stability, good water-processibility, satisfactory life-spans, superior electrocatalytic capacity with enzyme-like kinetic characteristics. The nanohybrid was applied as electrochemical sensors for single/simultaneous analysis of uric acid (UA), xanthine (XT) and hypoxanthine (HX). Excellent voltammetric responses for simultaneous determination in linear ranges of 0.1-800 µM with a limit of detection (LOD) of 0.052 µM for UA, 0.5-680 µM with a LOD of 0.021 µM for XT, and 0.7-320 µM with a LOD of 0.025 µM for HX under optimal conditions. Besides, the developed nanozyme sensor was employed for simultaneous voltammetric analysis of UA, XT and HX in real samples with acceptable recoveries. This work will provide theoretical guidance and experimental support for the preparation and application of two-dimensional materials, nanozymes and sensing devices.

Collision induced magnetic resonance in Cesium atoms.

The radiofrequency-optical double magnetic resonance in cesium atoms filled in a vapor cell is investigated experimentally. One resonant signal involving spin-exchange collisions is observed in the MZ type magnetic resonance spectrum. We solve Liouville equations describing the dynamics of the system and analyze the role of the spin-exchange collisions in the atomic population distributions under resonant conditions. The theoretical calculations agree very well with the experimental results. In contrast with the normal magnetic resonance, the collision induced magnetic resonance exhibits the interesting saturation effect: both the signal amplitude and the signal linewidth are nearly constant when the laser intensity is above a moderate threshold value, which can be useful for precision measurements of the geomagnetic field.

iASPP Is an Antioxidative Factor and Drives Cancer Growth and Drug Resistance by Competing with Nrf2 for Keap1 Binding.

Reactive oxygen species (ROS) have emerged as important signaling molecules that play crucial roles in carcinogenesis and cytotoxic responses. Nrf2 is the master regulator of ROS balance. Thus, uncovering mechanisms of Nrf2 regulation is important for the development of alternative treatment strategies for cancers. Here, we demonstrate that iASPP, a known p53 inhibitor, lowers ROS independently of p53. Mechanistically, iASPP competes with Nrf2 for Keap1 binding via a DLT motif, leading to decreased Nrf2 ubiquitination and increased Nrf2 accumulation, nuclear translocation, and antioxidative transactivation. This iASPP-Keap1-Nrf2 axis promotes cancer growth and drug resistance both in vitro and in vivo. Thus, iASPP is an antioxidative factor and represents a promising target to improve cancer treatment, regardless of p53 status.

Epigenetic silencing of ASPP1 confers 5-FU resistance in clear cell renal cell carcinoma by preventing p53 activation.

Inactivation of p53 has been shown to correlate with drug resistance in tumors. However, in clear cell renal cell carcinoma (ccRCC), p53 is rarely mutated, yet the tumors remain highly insensitive to the conventional chemotherapeutic drugs. The underlying mechanisms responsible for the non-genetic p53 inactivation remain obscure. Here, we report, for the first time, that Apoptosis Stimulating of P53 Protein 1 (ASPP1) was remarkably downregulated at both mRNA (about 3.9-fold) and protein (about 4.9-fold) levels in ccRCC human specimens in comparison with the paired normal controls. In addition, lower ASPP1 was closely related to the higher grade of tumors and shorter life expectancy of ccRCC patients, both with p < 0.001. We also find that CpG island hypermethylation at promoter region contributed to the suppression of ASPP1 expression in ccRCC that contained relatively low levels of ASPP1. Further functional studies demonstrated that forced expression ASPP1 not only significantly inhibited the growth rate of ccRCC, but also promoted sensitivity of ccRCC to the conventional chemotherapeutic drug 5-fluorouracil (5-FU)-induced apoptosis. Moreover, ASPP1 expression was accompanied with the apoptosis-prone alterations of p53 targets expression and p53 target PIG3 luciferase reporter activation. In contrast, ASPP1 knockdown promoted cell growth and prevent 5-FU-induced p53 activation and apoptosis. In conclusion, our results suggest that ASPP1 silencing is one of dominate mechanisms in inhibiting wild type p53 in ccRCC. ASPP1, therefore, may be potentially used as a promising biomarker for prognosis and therapeutic intervention in ccRCC.

EGR-1/ASPP1 inter-regulatory loop promotes apoptosis by inhibiting cyto-protective autophagy.

The decrease of ASPP1 (Apoptosis-Stimulating Protein of p53 1), a known p53 activator, has been linked to carcinogenesis and the cytotoxic resistance in various cancers, yet the underlying mechanisms of ASPP1 expression and its complex functions are not yet clear. Here, we report that ASPP1 forms an inter-regulatory loop with Early Growth Response 1 (EGR-1), and promotes apoptosis via inhibiting cyto-protective autophagy, independent of the well-documented p53-dependent mechanisms. We show that ASPP1 mRNA and protein were remarkably elevated by ectopic EGR-1 expression or endogenous EGR-1 activation, in cells with different tissue origins and p53 status. Conversely, RNAi-mediated EGR-1 knockdown suppressed ASPP1. The further mechanism studies revealed that ASPP1 promoter, mapped to -283/+88, which contained three conserved EGR-1 binding sites, was required for both binding and transactivity of EGR-1. In addition, we demonstrate that ASPP1 promoted EGR-1 in a positive feedback loop by preventing proteasome-mediated EGR-1 degradation or promoting EGR-1 nuclear import in response to anticancer natural compound Quercetin. Furthermore, albeit activating p53 in the nucleus is the well-studied function of ASPP1, we found that ASPP1 was predominately localized in the cytoplasm. Interestingly, the cytoplasmic ASPP1 retained its pro-apoptosis capability. Mechanistically, ASPP1 suppressed Atg5-Atg12 and also bound with Atg5-Atg12 to prevent its further complex formation with Atg16, resulting in the inhibition of cyto-protective autophagy. In conclusion, our results provide new insights into EGR-1/ASPP1 regulatory loop in sensitizing Quercetin-induced apoptosis. EGR-1/ASPP1, therefore, may be potentially used as therapeutic targets to improve cancer's response to pro-apoptosis treatments.