Disease relevance of Hsp22

• Genes for small heat shock proteins (hsp27 to hsp22) are activated in late third-instar larvae of Drosophila melanogaster in the absence of heat stress [1].

Psychiatry related information on Hsp22

• Moreover, flies expressing Hsp22 in their motorneurons maintain their locomotor activity longer as assessed by a negative geotaxis assay [2].

High impact information on Hsp22

• Downstream of the transcription start site in the Drosophila heat-shock gene hsp22, we have identified a region that is necessary for efficient transcription, and also for selective translation during heat shock [3].
• In contrast, hsp22 and hsp23 were found to be induced during aging at the RNA level and with a broader tissue distribution [4].
• Deletion analyses reveal that the 5' flanking sequences required for full expression of the hsp22 gene extend beyond the distal repeat [5].
• The D. melanogaster gene encoding the smallest heat shock protein, hsp22, contains within its 5' flanking sequences three such repeats, two close to the transcription start site and a distally located third one 101 base pairs further upstream [5].
• We have recently shown that overexpressing the mitochondrial Hsp22 increases Drosophila melanogaster lifespan by 32% and resistance to oxidative stress [6].

Biological context of Hsp22

• These observations establish Hsp22 as a key player in cell-protection mechanisms against oxidative injuries and aging in Drosophila and corroborate the pivotal role of mitochondria in the process of aging [2].
• By testing a series of 5' deletion mutants in hsp22/HSV-tk, a homologous sequence located adjacent to the TATA box in both the hsp22 and hsp26 genes was identified as being responsible for their heat-shock activation [7].
• Unique coding sequences for four heat shock proteins of Drosophila melanogaster, hsp 28, hsp 26, hsp 23, and hsp 22, are clustered in a 12-kilobase interval at chromosome subdivision 67B [8].
• Analysis of specific promoter mutations in transgenic flies indicated that functional heat shock response elements are required for hsp22 induction during aging [9].
• To determine if hsp22 and hsp23 gene expression might correlate with life span, RNA levels for these and additional genes were analyzed throughout the adult life span in a set of five outbred "O" lines, which have been genetically selected for increased longevity, and in five matched control "B" lines [10].

Anatomical context of Hsp22

• However other Hsps such as Hsp70 and Hsp22 were induced under heat-shock conditions in testes [11].
• During aging, hsp22 RNA was induced 60-fold in the head, with somewhat lower level induction in abdomen and thorax [9].
• HeLa cells containing the firefly luciferase (luc) reporter gene under the control of the Drosophila melanogaster hsp22 promoter were compared to liver cells (HepG2) containing the same stress gene promoter fused either to the luc or the EGFP (Enhanced-Green Fluorescent Protein) gene [12].

Associations of Hsp22 with chemical compounds

• The results indicate that relative to hsp22, the rate of hsp23 synthesis is significantly greater during recovery from heat shock and during ecdysterone induction [13].
• Here we examined the effects of histone deacetylase inhibitors (HDIs), trichostatin A, and sodium butyrate, on changes in acetylation level of core histones and on expression of hsp22 gene in Drosophila melanogaster [14].
• Doxycycline-regulated over-expression of hsp22 has negative effects on stress resistance and life span in adult Drosophila melanogaster [15].
• The hsp22 over-expression made flies more sensitive to heat and oxidative stress, while resistance to coumarin poisoning was not affected [15].

Other interactions of Hsp22

• The inhibition was highly specific: expression of the closely related heat shock proteins hsp22, hsp23, and hsp28 was unaffected [16].
• The heat shock transcriptional factor of Drosophila (DmHSF), present in significantly lower amount in testes when compared to other tissues such as the head, was shown to be required for the heat activation of Hsp22 and Hsp70 [11].
• The ability of Hsp90 mRNA to be preferentially translated is conferred by its 5'-UTR, but, in contrast to Hsp22 and -70, is primarily influenced by nucleotides close to the AUG initiation codon [17].
• This heat-shock RNA has the same cap site as the embryonic transcript, while its 3' portion entirely includes the neighbouring hsp22 gene [18].

Analytical, diagnostic and therapeutic context of Hsp22

• Immunoprecipitation results indicate that there is no interaction between DmHsp22 and the other small heat shock proteins [19].
• Fractionation of mitochondria indicates that DmHsp22 resides in the mitochondrial matrix, where it is found in oligomeric complexes, as shown by sedimentation and gel filtration analysis and by cross-linking experiments [19].
• By using the chromatin immunoprecipitation, we located the HDI-induced H3 hyperacetylation at both the promoter and the downstream of RNA polymerase II of the transcribing hsp22 gene [14].

References