Ask about this productRelated genes to: HCFC1R1 Blocking Peptide
- Gene:
- HCFC1R1 NIH gene
- Name:
- host cell factor C1 regulator 1
- Previous symbol:
- -
- Synonyms:
- HPIP, FLJ20568
- Chromosome:
- 16p13.3
- Locus Type:
- gene with protein product
- Date approved:
- 2003-06-23
- Date modifiied:
- 2016-03-21
Related products to: HCFC1R1 Blocking Peptide
Related articles to: HCFC1R1 Blocking Peptide
- While the role of endocytosis in focal adhesion turnover-coupled cell migration has been established in addition to its conventional role in cellular functions, the molecular regulators and precise molecular mechanisms that underlie this process remain largely unknown. In this study, we report that proto-oncoprotein hematopoietic PBX-interacting protein (HPIP) localizes to focal adhesions as well as endosomal compartments along with RUN FYVE domain-containing protein 3 (RUFY3) and Rab5, an early endosomal protein. HPIP contains two coiled-coil domains (CC1 and CC2) that are necessary for its association with Rab5 and RUFY3 as CC domain double mutant, that is, mtHPIPΔCC1-2 failed to support it. Furthermore, we show that HPIP and RUFY3 activate Rab5 by serving as noncanonical guanine nucleotide exchange factors of Rab5. In support of this, either deletion of coiled-coil domains or silencing of HPIP or RUFY3 impairs Rab5 activation and Rab5-dependent cell migration. Mechanistic studies further revealed that loss of HPIP or RUFY3 expression severely impairs Rab5-mediated focal adhesion disassembly, FAK activation, fibronectin-associated-β1 integrin trafficking, and thus cell migration. Together, this study underscores the importance of HPIP and RUFY3 as noncanonical guanine nucleotide exchange factors of Rab5 and in integrin trafficking and focal adhesion turnover, which implicates in cell migration. - Source: PubMed
Publication date: 2023/10/04
Khumukcham Saratchandra SinghPenugurti VasudevaraoBugide SureshDwivedi AnjuKumari AnitaKesavan P SKalali SruchythaMishra Yasaswi GayatriRamesh Vakkalagadda ANagarajaram Hampapathalu AMazumder AprotimManavathi Bramanandam - While phenotypic plasticity is a critical factor contributing to tumor heterogeneity, molecular mechanisms underlying this process are largely unknown. Here we report that breast cancer cells display phenotypic diversity in response to hypoxia or normoxia microenvironments by operating a reciprocal positive feedback regulation of HPIP and HIF-1α. We show that under hypoxia, HIF-1α induces HPIP expression that establishes cell survival, and also promotes cell migration/invasion, EMT and metastatic phenotypes in breast cancer cells. Mechanistic studies revealed that HPIP interacts with SRP14, a component of signal recognition particle, and stimulates MMP9 synthesis under hypoxic stress. Whereas, in normoxia, HPIP stabilizes HIF-1α, causing the Warburg effect to support cell growth. Concurrently, mathematical modelling corroborates this reciprocal feedback loop in enabling cell-state transitions in cancer cells. Clinical data indicate that elevated levels of HPIP and HIF-1α correlate with unfavorable prognosis and shorter survival rates in breast cancer subjects. Together, this data shows a reciprocal positive feedback loop between HPIP and HIF-1α that was unknown hitherto. It unveils how the tumor microenvironment influences phenotypic plasticity that has an impact on tumor growth and metastasis and, further signifies considering this pathway as a potential therapeutic target in breast cancer. - Source: PubMed
Publication date: 2021/11/09
Khumukcham Saratchandra SinghPenugurti VasudevaraoSoni AnitaUppala VeenaHari KishoreJolly Mohit KumarDwivedi AnjuSalam Pk AbdulPadala ChiranjeeviMukta SrinivasuluBhopal TriveniManavathi Bramanandam - While cancer cells rewire metabolic pathways to sustain growth and survival under metabolic stress in solid tumors, the molecular mechanisms underlying these processes remain largely unknown. In this study, cancer cells switched from survival to death during the early to late phases of metabolic stress by employing a novel signaling switch from AMP activated protein kinase (AMPK)-Forkhead box O3 (FOXO3a)-hematopoietic PBX1-interacting protein (HPIP) to the ring finger protein 2 (RNF2)-HPIP-ubiquitin (Ub) pathway. Acute metabolic stress induced proto-oncogene HPIP expression in an AMPK-FOXO3a-dependent manner in breast cancer (BC) cells. HPIP depletion reduced cell survival and tumor formation in mouse xenografts, which was accompanied by diminished intracellular ATP levels and increased apoptosis in BC cells in response to metabolic (glucose) stress. Glutamine flux (C-labeled) analysis further suggested that HPIP rewired glutamine metabolism by controlling the expression of the solute carrier family 1 member 5 (SLC1A5) and glutaminase (GLS) genes by acting as a coactivator of MYC to ensure cell survival upon glucose deprivation. However, in response to chronic glucose stress, HPIP was ubiquitinated by the E3-Ub ligase, RNF2, and was concomitantly degraded by the proteasome-mediated pathway, ensuring apoptosis. In support of these data, clinical analyses further indicated that elevated levels of HPIP correlated with AMPK activation in BC. Taken together, these data suggest that HPIP is a signal coordinator during metabolic stress and thus serves as a potential therapeutic target in BC. - Source: PubMed
Publication date: 2021/07/22
Penugurti VasudevaraoKhumukcham Saratchandra SinghPadala ChiranjeeviDwivedi AnjuKamireddy Karthik ReddyMukta SrinivasuluBhopal TriveniManavathi Bramanandam - Hematopoietic PBX interacting protein (HPIP or pre-B-cell leukemia transcription factor interacting protein (PBXIP1) was discovered two decades ago as a corepressor of pre-B-cell leukemia homeobox (PBX) 1 with a vital functional role in hematopoiesis. Later it emerged as a potential biomarker of poor prognosis and tumorigenesis for more than a dozen different cancers. It regulates aggressive cancer phenotypes, cell proliferation, metastasis, EMT, etc. The anomaly in the regulation of HPIP is linked with physiological disorders like renal fibrosis, chronic kidney disease and osteoarthritis. Scientists have unraveled more than twenty interacting proteins of HPIP and its functional role in various physiological and cellular processes that involves normal neuronal development, embryogenesis, endometrium decidualization, and germ cell proliferation. Over the past 20 years, we have witnessed the emerging role of HPIP and its association with a myriad of cellular activities ranging from germ cell proliferation to cancer aggressiveness, modulating multitude of signaling cascades like TGF-β1, PI3K/AKT, Wnt, mTOR, and Sonic hedgehog signaling pathways. This review will give the current understanding of HPIP, in terms of its diverse functions, theoretical ideas, and further explore cellular links and promising areas that need to be investigated. We also provide a comprehensive overview of the transcript variants of HPIP and distinct sets of transcription factors regulating their expression, which may help to understand the role of HPIP in various cellular or physiological conditions. - Source: PubMed
Publication date: 2021/06/05
Khumukcham Saratchandra SinghManavathi Bramanandam - Hematopoietic pre-B-cell leukemia transcription factor (PBX)-interacting protein (HPIP) has shown to be overexpressed in several human cancers. The purpose of this study was to explore the expression of HPIP in endometrial cancer (EC) and its associated effects on disease. - Source: PubMed
Publication date: 2019/06/26
Cheng LiZhao TingtingLi ShiguoWang YaoFei HuiMeng Fanling