title: ΔN-ASPP2, a novel isoform of the ASPP2 tumor suppressor, promotes cellular survival.
abstract: ASPP2 is a tumor suppressor that works, at least in part, through enhancing p53-dependent apoptosis. We now describe a new ASPP2 isoform, ΔN-ASPP2, generated from an internal transcription start site that encodes an N-terminally truncated protein missing a predicted 254 amino acids. ΔN-ASPP2 suppresses p53 target gene transactivation, promoter occupancy, and endogenous p53 target gene expression in response to DNA damage. Moreover, ΔN-ASPP2 promotes progression through the cell cycle, as well as resistance to genotoxic stress-induced growth inhibition and apoptosis. Additionally, we found that ΔN-ASPP2 expression is increased in human breast tumors as compared to adjacent normal breast tissue; in contrast, ASPP2 is suppressed in the majority of these breast tumors. Together, our results provide insight into how this new ASPP2 isoform may play a role in regulating the ASPP2-p53 axis.
authors.affiliation: Department of Medicine, Division of Hematology and Medical Oncology and the Knight Cancer Institute, Oregon Health and Science University, Portland, OR 97239, USA.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Van Hook
authors.affiliation: Department of Medicine, Division of Hematology and Medical Oncology and the Knight Cancer Institute, Oregon Health and Science University, Portland, OR 97239, USA.
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Medicine, Division of Hematology and Medical Oncology and the Knight Cancer Institute, Oregon Health and Science University, Portland, OR 97239, USA; Beijing Institute of Hepatology, Beijing You'an Hospital, Capital Medical University, Beijing, 100069, China.
authors.forename: Dexi
authors.initials: D
authors.lastname: Chen
authors.affiliation: Department of Medicine, Division of Hematology and Medical Oncology and the Knight Cancer Institute, Oregon Health and Science University, Portland, OR 97239, USA.
authors.forename: Casey
authors.initials: C
authors.lastname: Nold
authors.affiliation: Department of Medicine, Division of Hematology and Medical Oncology and the Knight Cancer Institute, Oregon Health and Science University, Portland, OR 97239, USA.
authors.forename: Zhiyi
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: Department of Molecular and Medical Genetics and the Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97239, USA.
authors.forename: Pavana
authors.initials: P
authors.lastname: Anur
authors.affiliation: Department of Medicine, Division of Hematology and Medical Oncology and the Knight Cancer Institute, Oregon Health and Science University, Portland, OR 97239, USA.
authors.forename: Hun-Joo
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Shandong Tumor Hospital and Institute, Jinan, 250117, China.
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Yu
authors.affiliation: Department of Surgery and the Knight Cancer Institute, Oregon Health and Science University, Portland, OR 97239, USA.
authors.forename: Brett
authors.initials: B
authors.lastname: Sheppard
authors.affiliation: Department of Molecular and Medical Genetics and the Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97239, USA.
authors.forename: Mu-Shui
authors.initials: MS
authors.lastname: Dai
authors.affiliation: Department of Molecular and Medical Genetics and the Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97239, USA.
authors.forename: Rosalie
authors.initials: R
authors.lastname: Sears
authors.affiliation: Department of Molecular and Medical Genetics and the Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97239, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Spellman
authors.affiliation: Department of Medicine, Division of Hematology and Medical Oncology and the Knight Cancer Institute, Oregon Health and Science University, Portland, OR 97239, USA. Electronic address: lopezc@ohsu.edu.
authors.forename: Charles D
authors.initials: CD
authors.lastname: Lopez
mesh_terms: D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000737:chemistry* / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D003001:Cloning, Molecular; D004249:DNA Damage; D005260:Female; D006801:Humans; D051379:Mice; D000072417:Protein Domains; D015533:Transcriptional Activation; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000737:chemistry*
chemical_list: D051017:Apoptosis Regulatory Proteins; C495901:TP53 protein, human; C090468:TP53BP2 protein, human; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins
keywords: ASPP2; Tumor suppressor; p53