Pancreatic Cancer

• Chmp 1A is a mediator of the anti-proliferative effects of All-trans Retinoic Acid in human pancreatic cancer cells [1].
• Chmp1A functions as a novel tumor suppressor gene in human embryonic kidney and ductal pancreatic tumor cells [2].
• Chromatin modifying protein 1A (Chmp1A) of the endosomal sorting complex required for transport (ESCRT)-III family activates ataxia telangiectasia mutated (ATM) for PanC-1 cell growth inhibition [3].

Disease relevance of CHMP1A

• A total of seven known genes, including PRSM1, PISSLRE, and the recently cloned Fanconi anemia A (FAA) gene, and potential transcripts from exon-trapping experiments have been located to this contig [4].
• There is good harmonisation among the recommendations and requirements although the EU CHMP guideline calls for greater attention to be paid to the potential presence of infectious bovine polyoma virus [5].

High impact information on CHMP1A

• In mammals, CHMP1 functions in the pathway targeting plasma membrane receptors and ligands to lysosomes for proteolytic degradation [6].
• The sal1 gene encodes a homologue of the human Chmp1 gene, a member of the conserved family of the class E vacuolar protein sorting genes implicated in membrane vesicle trafficking [6].
• Similar to the action of a mutant SKD1 protein, overexpression of a fusion derivative of human CHMP1 dilates endosomal compartments and disrupts the normal distribution of several endosomal markers [7].
• CHMP1 can recruit a PcG protein, BMI1, to these regions of condensed chromatin and can cooperate with co-expressed vertebrate Pcl in a Xenopus embryo PcG assay; this is consistent with a role in PcG function [8].
• We have constructed a stable HEK293 cell line that inducibly overexpresses CHMP1 under ecdysone control [8].

Biological context of CHMP1A

• In contrast the human genome encodes 10 homologous proteins (CHMP1A (approved gene symbol PCOLN3), 1B, 2A, 2B, 3 (approved gene symbol VPS24), 4A, 4B, 4C, 5, and 6) [9].
• In combination, these observations suggest that CHMP1 plays a role in stable gene silencing within the nucleus [8].
• CHMP1 is a novel nuclear matrix protein affecting chromatin structure and cell-cycle progression [8].
• In a screen for conserved partners of the PcG protein Polycomblike (Pcl), we have identified a new protein, human CHMP1 (CHromatin Modifying Protein; CHarged Multivesicular body Protein), which is encoded by an alternative open reading frame in the PRSM1 gene and is conserved in both complex and simple eukaryotes [8].
• PRSM1 could share sequence homology with the type III procollagen N-proteinase [10].

Anatomical context of CHMP1A

• Thus, the final steps in the budding process may include CHMP protein polymerization and lattice formation on membranes by employing different bilayer-recognizing surfaces, a function shared by all CHMP family members [11].

Analytical, diagnostic and therapeutic context of CHMP1A

• Molecular cloning, expression and chromosomal localization of a human gene encoding a 33 kDa putative metallopeptidase (PRSM1) [10].

References