Marwa
Abdel-Hak
Science and Engineering 84 Program for Research in Science and Engineering Proteasomal Regulation of Nuclear Hormone Receptors
Abstract profile. Full document pending author claim.
Authors:
Marwa Abdel-Hak, Wallace Wong, Jonathan Tsai
Date Created:
2025-01-01
Course Title:
Professor:
Not specified
About Paper:
Nuclear hormone receptors (NRs) are ligand-activated library to assess PSMD14’s interactions with each NR. We are transcription factors that regulate gene expression in response chemically and genetically inhibiting PSMD14, and will quantify to small signaling molecules. Mechanisms to promote NR receptor levels to identify candidates that may be stabilized. As a degradation have been widespread in clinical use. PSMD14, a future direction, receptors found to be stabilized may be analyzed proteasomal deubiquitinase, typically facilitates degradation by for shared residues or domains that mediate interaction with removing ubiquitin chains from substrates just before proteasome PSMD14. Thisworkaimstoclarifyreceptor-specificregulationby entry. However, preliminary findings suggest that PSMD14 may PSMD14 and inform new strategies for targeting hormone-driven instead stabilize certain NRs, indicating a noncanonical role. To diseases and treatment-resistant cancers. investigate this, we are screening a nuclear receptor expression Investigating PCMTD1 Substrate Preferences for an Improved Understanding of Cellular Proteostasis Audric Adonteng, Abigail Porter, Christina Woo Harvard College | Eliot House | Chemistry | 2028 Protein deamidation, a form of post-translational modification, degradation. To examine this, we synthesized a peptide library occurs in the process of cellular aging and disrupts the chemical derived from a known PCMTD1-binding sequence, introducing composition of proteins. Specifically, protein deamidation single alanine substitutions at each position, characterizing generates isoaspartate (isoAsp), an amino residue introducing a the library by mass spectrometry and high-performance liquid methylene group to disrupt the peptide backbone. PCMTD1, a chromatography. To quantify the protein-peptide interactions, we substraterecognitioncomponentofanE3ubiquitinligasecomplex, adapted a time-resolved fluorescence resonance energy transfer selectively recognizes proteins bearing isoAsp residues and is assayforPCMTD1. Usingcompetitivedisplacementofthepeptide predicted to facilitate their degradation. With research suggestinlibrary, we ranked the binding affinities across different peptide that isoAsp accumulation is linked to Alzheimer’s disease, a sequences through comparison of dissociation constants derived deeper understanding of PCMTD1 may reveal therapeutic targets from these emission signals, determining which positions are to mitigate neurodegenerative disease progression. Currently, the crucial for PCMTD1 recognition. By identifying the sequence substratebindingpreferencesthatgovernwhichproteinsPCMTD1 preferences of PCMTD1, this research lays the groundwork marks for degradation remain unknown. We hypothesize that for validating findings in live cell models and understanding PCMTD1 exhibits distinct sequence-dependent preferences for its endogenous protein substrates. These insights may inform residues surrounding isoAsp. Thus, the objective of this study therapeutic strategies to reduce the accumulation of damaged is to profile the sequence preferences of PCMTD1 to determine proteins associated with neurodegenerative diseases. the motifs that enhance or inhibit substrate recognition for QualitativeStudyofPeerSupportPreferencesAmongCaregiversofPatients
Abstract:
Nuclear hormone receptors (NRs) are ligand-activated library to assess PSMD14’s interactions with each NR. We are transcription factors that regulate gene expression in response chemically and genetically inhibiting PSMD14, and will quantify to small signaling molecules. Mechanisms to promote NR receptor levels to identify candidates that may be stabilized. As a degradation have been widespread in clinical use. PSMD14, a future direction, receptors found to be stabilized may be analyzed proteasomal deubiquitinase, typically facilitates degradation by for shared residues or domains that mediate interaction with removing ubiquitin chains from substrates just before proteasome PSMD14. Thisworkaimstoclarifyreceptor-specificregulationby entry. However, preliminary findings suggest that PSMD14 may PSMD14 and inform new strategies for targeting hormone-driven instead stabilize certain NRs, indicating a noncanonical role. To diseases and treatment-resistant cancers. investigate this, we are screening a nuclear receptor expression Investigating PCMTD1 Substrate Preferences for an Improved Understanding of Cellular Proteostasis Audric Adonteng, Abigail Porter, Christina Woo Harvard College | Eliot House | Chemistry | 2028 Protein deamidation, a form of post-translational modification, degradation. To examine this, we synthesized a peptide library occurs in the process of cellular aging and disrupts the chemical derived from a known PCMTD1-binding sequence, introducing composition of proteins. Specifically, protein deamidation single alanine substitutions at each position, characterizing generates isoaspartate (isoAsp), an amino residue introducing a the library by mass spectrometry and high-performance liquid methylene group to disrupt the peptide backbone. PCMTD1, a chromatography. To quantify the protein-peptide interactions, we substraterecognitioncomponentofanE3ubiquitinligasecomplex, adapted a time-resolved fluorescence resonance energy transfer selectively recognizes proteins bearing isoAsp residues and is assayforPCMTD1. Usingcompetitivedisplacementofthepeptide predicted to facilitate their degradation. With research suggestinlibrary, we ranked the binding affinities across different peptide that isoAsp accumulation is linked to Alzheimer’s disease, a sequences through comparison of dissociation constants derived deeper understanding of PCMTD1 may reveal therapeutic targets from these emission signals, determining which positions are to mitigate neurodegenerative disease progression. Currently, the crucial for PCMTD1 recognition. By identifying the sequence substratebindingpreferencesthatgovernwhichproteinsPCMTD1 preferences of PCMTD1, this research lays the groundwork marks for degradation remain unknown. We hypothesize that for validating findings in live cell models and understanding PCMTD1 exhibits distinct sequence-dependent preferences for its endogenous protein substrates. These insights may inform residues surrounding isoAsp. Thus, the objective of this study therapeutic strategies to reduce the accumulation of damaged is to profile the sequence preferences of PCMTD1 to determine proteins associated with neurodegenerative diseases. the motifs that enhance or inhibit substrate recognition for QualitativeStudyofPeerSupportPreferencesAmongCaregiversofPatients
Source:
Harvard / Howard University | Economics | 2026 / 2025
Topics:
pcmtd1, protein, psmd14, receptor, degradation, sequence, residue, substrate, disease, preference, isoasp, nuclear
